We evaluated the disposition kinetics of taxanes, an antitumor agent after the intraperitoneal administration in nine patients with peritoneal tumors. The intraperitoneal concentrations of docetaxel or paclitaxel decreased slowly following the i.p. infusion administration of either docetaxel (60-80mg/day) or paclitaxel (120-180mg/ day) over a 1-hour period in patients. There was no difference in the concentration-time courses between both drugs in each patient, and the elimination half-time was about 8hr. The area under the intraperitoneal concentration-time curve (AUCp) of paclitaxel relative to the dose was about 3-times larger than that of docetaxel. On the other hand, the permeability of these drugs from the peritoneal cavity into the systemic circula-tion was extremely small. The plasma concentrations and the AUCs of both drugs showed large individual variations among the patients. The ratios of AUCs/AUCp of docetaxel and paclitaxel relative to the dose were 7.1 ×10^-2and 3.8×10^-3, respectively. The permeability of paclitaxel was only about 1/20 that of docetaxel.

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An improvement in the utilization of medical devices and instruments is important in order to prevent medical accidents from a viewpoint of human engineering. However, it is much important to prevent any operations of health care practitioners which may cause such accidents. In this study, we evaluated the risk involved with the injection of drugs in order to prevent medical accidents by the misuse of medical devices.
First, a risk evaluation was performed. Next, the administration of drugs by 5 nurses and pharmacists was recorded by VTR in order to analyze the administration and length of time required. In addition, the ampule method was compared with the pre-filled syringe (PFS) method. Regarding the risk evaluation, the patient risk and worker risk related to the PFS method was respectively about 1/4 lower and about 1/3 lower than with the ampule method. Regarding the administration time, a 60% decrease in the administration time was observed for pharmacists but for nurses the decrease was slight.
The PFS method was thus found to be clearly more effective than the ampule method for the prevention of medical accidents, related to human error. However, risk associated with human error cannot be completely removed even when using the PFS method. Problems still remain regarding mix-ups with drugs, injuries suffered by health care practitioners, and bacteria contamination due to inadvertent needle stabs.
In conclusion, the PFS method had excellent results regarding administration efficiency and safety, while it increased the amount of the medical wastes.

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The susceptibilities of various antiseptics toStaphylcoccus aureuscarrying antiseptic-resistance genes, qacA, smr and/or mutatednorA, were evaluated by a method to determine the minimum bactericidal concentration (MBC) and the minimum inhibitory concentration (MIC). In benzalkonium chloride, benzethonium chloride and alkydiaminoethylglycine hydrochloride, which are used for the washing of hands, skin-surfaces and wounds, we observed, in terms of MIC, no clear difference between the strains with and without antiseptic-resistance gene (s). However, we found that, in the modified method of MBC using a neutralizer, antiseptic-resistant strains survived after exposure to those antiseptics for 5 min at the minimum standard concentration (100μg/mL). The results showed that S.aureusstrains carrying antiseptic-resistance gene (s) exhibited resistance to various antiseptics. Therefore, the modified determination of MBC was thus found to be useful for evaluating the susceptibility of antiseptics to antiseptic-resistant S.aureus.

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Over 100 pharmaceutical products are withdrawn from the market in Japan each year. Nonetheless, there has so far been no report consisting of a specific survey of the volume of work borne by the medical organizations related to such with drawals. As are sult, a survey of the response of medical organizations and the volume of work have been made regarding the withdrawal of Maalox ^®in August 2000.
Our findings revealed that a considerable amount of time, namely 4, 502 minutes was expended regarding the withdrawal of this product at Kitasato University East Hospital. A total of 2, 770 minutes, or 62% of the total time was spent within 24 hours after receiving the announcement of the drug's removal from the market. When the total time was broken down by job type, 3, 188 minutes, or 71% of the total, were spent by pharmacists A further, 2, 315 minutes, or 52% of the total, were used to determine how to best respond to the matter.
In order to efficiently recall pharmaceutical products, an operation was established which was thereafter distributed to all concemed staff members.
The total time spent on the withdrawal of Maalox ^® was estimated to have utilized approximately ¥285, 000of labor cost, based on the average wages of the employees. As a result, hospitals are forced to bear a significant economic burden whenever such products are withdrawn.
Finally, pharmaceutical manufacturers should be equipped with the systems for manufacture and supply as much as possible to minimize such recall incidents. When drug are unavoidably withdrawn, however, the manufacturers should nevertheless provide all appropriate information as quickly as possible to the related medical organizations while carefully taking the economic burden that such organizations must bear into consideration.

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On December 27, 2000, the Ministerial Ordinance No. 151, and the Notification from Pharmaceutical and Medical Safety Bureau Director of the Ministry of Health and Welfare (No. 1324) were issued. As a result, the requirement to collect up to 3, 000 examples for PMS (Post Marketing Surveillance) became unnecessary, and intensive investigations for six months right after sale will instead be conducted. Although conducting such investigations right after marketing is necessary in order to complete a “side effects and an infection report”, various problems are still remain.
In view of these situations, the pharmacists at our hospital took the lead in implementing the investigation right after marketing in order to identify the effects and estimate the man power and cost for medical institutions. This paper also compares the efficiency of various methods to collect adverse events between pharmacists and MR individuals. Moreover, some future subjects identified from the present investigation process are discussed on.
Investigations right after marketing was conducted by collecting institutional questionnaires issued to physicians with four medicines for two or three months this time. The effect of such investigations (influence to the rapidity and certainty with collecting of adverse events) regarding intervention by the pharmacists was found to be large. In particular, the effect remarkably increase as a large number of questionnaires issued. It became clear that man power and cost were largely proportional to the number of collected questionnaires rather than the frequency of adverse events.
Calculating the cost as a means of evaluating the value equivalent to these new jobs on monitoring adverseevents from now on is indispensable. If the route for an adverse event and/or side effect with a new medicine could be monitored and coped with is not made promptly, then, the reliability of a medical institution could be greatly affected. In this meaning, pharmacists have to accumulate the implementation results of these investigations in their own medical institution.

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An α-Glucosidase inhibitor, acarbose, offers a novel approach in the treatment of diabetes mellitus. Although several symptoms of the digestive system are known to be side effects of acarbose, severe hepatic disease has also been reported. In this case, the alanine aminotransferase (ALT) level was observed to progressively increase after the administration of acarbose. There is little doubt that the patient suffered a drug-induced hepatic injury. In order to clarify the etiology of this increase in ALT, a drug-induced lymphocyte stimulation test and hepatitis virus marker test were performed and the administration of acarbose was discontinued. All laboratory tests showed negative results, and at 40 days after the administration, the ALT level was found to be near the normal range. A clinical pharmacist should monitor the parameters to assess the response and to document the absence of any side effects.

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We surveyed some significant factors related to the use of generic drugs, such as the stability of supply, the timeliness of package insert revisions, the existence and/or contents of “Interview Forms” (IF), the unit sizes and the locations of marketing offices. The drugs on which information was collected for this survey were 1) those normal carried by our hospital and had generic equivalents, and 2) those among the top 5 products both in terms of the frequency of prescriptions written and in terms of the total value of requested NHI reimbursements.
As a result we found the following information on the drugs studies : the products were sold through a direct sales route that did not involve a wholesaler, package inserts were less revised than the original drugs, IFs were not provided or, if they were, the contents were not sufficient (often not even easily obtainable data or references), the smallest unit provided were larger than the original drugs', and the manufacturers of generic equivalents did not have branch offices in the same prefecture as our hospital.
The product quality of the drugs remains a very important factor. However, in addition to the price, a stable source of supply for all drugs from which prompt delivery of the drug itself, as well as adequate product information are needed to ensure the safe and appropriate use of the products. As a result of the above investigations, the overall growth of the Generic Drug Market is expected to increase in the near future.

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Rebamipide, an antiulcer drug, has been reported to possess an antioxidant effect and to restore the impairment of antioxidants in experimental colitis. Recently, a rebamipide rectal suspension enema has been investigated as one type of pharmacotherapy to treat ulcerative colitis (UC). This enema has been prepared in house, but its stability has not yet been examined. In our hospital, we prescribe a drug for which its stability is unknown for only a short period. This enema could not be prescribed with other drugs that could be prescribed for a longer period. As a result, such patients have come to the hospital frequently, which makes the treatment regimen more difficult. We determined the contents of rebamipide contained in the enema using HPLC, and observed no significant changes after 5 weeks of storage, which thus made its longer-term prescription possible. We also experienced a patient with moderate rectal UC who encountered adverse effects related to steroid treatment. While tapering the dosage of steroids, we administered the rebamipide rectal suspension enema, and the patient responded well to the agent.

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Doses of tacrolimus less than the standard dose (0.5mg) have often been prescribed for pediatric transplantpatients. When preparing 0.1mg tacrolimus in a package, 13mg (contain 0.1mg tacrolimus) was used with a 0.5mg Prograf® capsule (the total amount of 65mg), and then it was packaged by hand. However, it is difficult to prepare such drugs for many transplant patients, since this method is very complicated. Therefore, we examined how to prepare low dose packages of tacrolimus package easily and correctly without making any packaging errors. To reduce any preparation errors, the bulk of tacrolimus was increased by mixing it with lactose. The contents of tacrolimus in the prepared package and the blood of patient were measured using the microparticle enzyme immunoassay (IMX). When mixing the medicine and lactose, the mixing errors using a sieve were fewer than when using a mortar and pestle. Regarding package errors (CV), packaging by hand resulted in fewer errors than when using an automatic packaging machine. Moreover, the preparation time of packaging significantly decreased when using this method, in comparison to the conventional method, and no difference was found in the blood concentration of tacrolimus in pediatric liver transplant patients, who took the medicine prepared by both conventional and the present methods. Therefore, when drugs need to be packaged at doses lower than the standard doses, such drugs should be mixed by a sieve and then be packed by hand to reduce preparation errors.

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In general, medical staff members do their utmost to select appropriate medicines for each patient whenever possible. When choosing medicines, pharmacists have to provide medical staff members and patients with high quality information. However, it is often difficult to select the optimal medicine for patients. When physicians in Intensive Care Unit (ICU) and chief physicians select medication, how do they obtain mutual consent, and what kind of drugs are readily provided by mutual agreement ? We tried to investigate this point using a questionnaire against given to both physicians and chief physicians in ICUs.
Physicians in ICU and chief physicians were requested to fill in questionnaires regarding how they selectinjection preparations in terms of purpose, reason and expectations of efficacy in order to inject preparations which are used with high frequency in ICU.
As a result, three factors when selecting injection preparations were found to vary among the physicians depended on the medications. These three factors were closely correlated with the injection preparations for the circulatory system since it was easy to evaluate their effects. However, when selecting dopamine and furosemide (20mg), disagreements often arouse even when there was agreement on the purpose and expectations of the drug.
The effects of other injection preparations are difficult for physicians in ICU and chief physicians to evaluate because they are often used for different purposes. For example, pirenzepin was found to be continually used even though its effects were unclear.
These results suggest that purposes and reasons for using injection preparations and the expectations of efficacy do not always correlate between ICU physicians and chief physicians, even though they may hold a meeting to discuss such drug selection in the ICU. As a results, it is important that pharmacists provide information based on evidence for selecting medicines in order to promote the appropriate and rational use of medicines in ICU.

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The effect and necessity of antimicrobial agents in preventing postoperative infections have been variously reported in the literature. Based on the results of these studies, prophylactic antimicrobial agents were administrated prior to operations. However, postoperative infections, major postoperative complications, can pose a serious clinical problem.
Using a retrospective analysis, the risk factors for postoperative infections were investigated in the following patients : those undergoing primary coronary artery bypass grafting on-pump (CABG : N=168) and others undergoing the same procedure off-pump (OPCAB : N=398).
To clarify the risk factors, each patient was assigned to one of the following 2 groups : those treated with cefazolin (CEZ) both before and after surgery and those who received other antibiotics instead of CEZ after surgery. The parameters recorded for each patient were as follows :
(1) Factors related to the patient : age, gender, WBC on postoperative day 3, a complication of diabetes mellitus (DM), and preoperative findings, including the total cholesterol level, uric acid level, serum albumin content, blood hemoglobin concentration, blood product use, New York Heart Association classification of cardiac patient, Ejection Fraction, and creatinine clearance (C-Cr).
(2) Factors related to the surgical procedures : the time required for surgery, aortic cross-clamping time, duration of extracorporeal circulation, variation in the use of the internal thoracic artery, duration of use of a drainage tube, and the nature of the operation (emergency or elective).
Significant variations were noted for some of these parameters. More significant differences were noted regarding the time required for surgery (on-pump CABG, OPCAB : p< 0.01), complications by DM (on-pump CABG : p<0.05, OPCAB : p<0.01) and WBC on postoperative day 3 (on-pump CABG, OPCAB : p<0.01). The Goal is to present the results of this study to physicians and recommend their incorporation into a design when developing future clinical paths.

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The administration of medicine using a nasogastric tube is occasionally used in epileptic patients with dysphagia. Such a tube occludes more frequently in pediatric patients than in adults, since the diameter of tube for a child is smaller than that for an adult. We therefore examined the passage of 28 medicines (13 antiepileptic drugs, 10 antibiotics, 2 medicine for intestinal disorders and 3 others) commonly used in pediatric epilepsy patients through a nasogastric tube for pediatric patients. The occlusion of the tube by medicines depended on the solubility and suspension of the medicine but not on the dosage form such as either fine powders or granules. The occlusion of the tube improved by the powderization of the medicine or increasing the diameter of the tube. Although some medicine did stick to the inner wall of the tube, such attachment was removed by washing out the tube with water. Providing this information to the doctor facilitated the rational prescription planning by confirming the diameter of tube and the medicine of the patients. In addition, the results of the current study are useful for pharmacists since they help in providing improved pharmaceutical care and counseling for pediatric epilepsy patients using a nasogastric tube.

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Benzalkonium chloride is most commonly used as a preservative for ophthalmic solutions at a dosage of 50 μg/mL. In this study, we evaluated the antibacterial activity of this preservative against 16 species and64 clinically isolated strains. Benzalkonium chloride demonstrated a good effect on gram-positive cocci, the minimum inhibitory concentrations (MICs) of benzalkonium chloride to Staphylococcus epidermidis and Staphylococcus aureus including MRSA were less than 12.5μg/mL. On the other hand, benzalkonium chloride was not effective against gram-negative rods ; 95% (42/44) of gram-negative rods strains were not susceptible after treatment with 50μg/mL of benzalkonium chloride. Especially, the MICs of benzalkonium chloride to clinically isolated pseudomonas aeruginosa were over 200μg/mL. These results suggest that benzalkonium chloride as preservative for ophthalmic solutions in effective on gram-positive cocci even when used in concentrationsonly one fourth times as much as those commercially available and to gram-negative rods when used in concentrations which may cause damage to the comeas. The use of lower concentration of benzalkonium chloride may therefore make it possible to reduce the degree of damage to the cellular components of the cornea.

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A “Drug information brochure for inpatients undergoing CHOP therapy” was prepared in order to minimize inter-individual difference in pharmaceutical care and drug consultation by clinical pharmacists and to ensure the accurate understanding of the patients. The CHOP regimen has been conducted as the standard method for the treatment of non-Hodgikin's lymphoma. The draft version of the brochure was prepared based on information provided by the pharmaceutical companies and from the literature in advance, and the brochure was revised after the drug consultations by clinical pharmacists, especially through the monitoring of any adverse events. The revisions included the time period when adverse events might be encountered ; and the methods to help the patients cope with such adverse events, the initial symptoms of such adverse events, and other potential problems. By using this brochure, clinical pharmacists could conduct the drug consultation more effectively and accurately while also ensuring that patients obtained a maximum understanding of the CHOP therapy regimen.

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Nifekalant hydrochloride, a class III antiarrhythmic agent, has recently been placed on the market in Japan. Since its solubility is poor in solutions above pH 6, it is predicted that when nifekalant hydrochloride is dissolved in such solutions at high concentrations, some crystallization may occur. Crystallization of nifekalant and changes in pH were observed when 0.1N-sodium hydroxide solution was added at concentrations of 2, 3, 4, and 5% to a nifekalant hydrochloride solution in either normal saline or 5% glucose. To evaluate the effect of fresh blood on the crystallization of nifekalant, nifekalant or lidocaine (for comparisons with nifekalant), concentrations in the upper layer and clot of blood were measured after fresh blood and nifekalant or lidocaine solution at concentrations of 1, 2.5, 5 and 10mg/mL, respectively. As a result, the more the pH or concentration increased, the greater the degree of crystallization of nifekalant in the solution with a pH between 5.5 and 6.5. The concentration of lidocaine in the upper layer was the same in each solution. Although the concentrations of nifekalant in the upper layer did not differ in the solutions with concentrations of 1 and 2.5mg/mL, remarkable decreases in the concentration of nifekalant in the upper layer were observed in the solutions with concentrations of 5 and 10mg/mL. On the other hand, remarkable increases in the concentration of nifekalant in the clot of blood were observed in the solution with a concentration of 5 and 10mg/mL and crystallizations of nifekalant were observed in specimens of the clots. These results suggested that when a nifekalant injection is administered it should not be mixed with solutions demonstrating a pH level above 5.5 and such concentrations must be maintained at a volume of less than 2mg/mL.

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Sustained release oral formulations, which have various advantages such as a reduction in number of doses and the prevention of side effects by suppressing a rapid increase in blood level of drugs, are broadly used for medication. Although these formulations are frequently prescribed, their usage does not always correlation with the indications. One of the reasons for this problem is due to insufficient communication between the makers (pharmaceutical company) and the users (medical institution).
We surveyed the present usage of prescribed sustained release oral formulations at medical institutions. We then sent a questionnaire to both pharmaceutical companies and medical institutions (pharmacists) based on the investigation results. As a result, both groups generally agreed regarding the efficacy of sustained release oral formulations, while they have different points of view regarding the advantage of using these formulations. Pharmacists agreed that sustained release oral formulations could be administered with slight modifications in the prescription depending on each patient's particular condition. In contrast, R & D workers in pharmaceutical companies strongly believed that there should be no changes in the prescribed dosage regimen. It is important to clarify and understand the similarities and differences for both sides regarding the usage of sustained release oral formulations. The obtained result may lead to a more effective usage of such medications.

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Oral rapid disintegrating tablets are taken in an epochal dosage form which makes drug ingestion less trou-blesome for patients. It has indeed contributed a great deal to an improvement in the quality of health care. On the other hand, however, rapid disintegrating tablets are more vulnerable to physical impact than uncoated tablets so that one-dose packages of oral rapid disintegrating tablets may present problems when being dispensed by a fully automatic tablet packing machine. The present study was conducted to evaluate the suitability to automatic mechanical dispensing of Enalapril M Tablet 5mg EMEC® and Brotizolam M Tablet 0.25mg EMEC® (rapid disintegrating tablets produced from Elmed Eisai Co., Ltd., that have been developed in dosageforms amenable to automatic mechanical dispensing) by 18 pharmacists.
The rejection rate was a meager 0.3% for both Enalapril and Brotizolam tablets. Errors occurred with a higher frequency when the rotor cassette was loaded in a mid-position than at another position. The results of experimental dispensing suggested that the greater the degree of the hardness or the heavier the weight of the tablets, the less damage that was done to them and thus the higher the rate of acceptance. When Enalapril® was administered with different tablets together, the relative rate of acceptance was Zyloric® > Amlodin® > Mevalotin®. When Brotizolam was administered with Depas®, a high rate of acceptance was shown, but when it was dispensed with Etizolam, it showed a low rate of acceptance, and its packages also contained many damaged tablets.

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Acarbose, an α-glucosidase inhibitor, is a well-established treatment of diabetes mellitus. Unfortunately, acarbose has one very frequent side effect, namely increased flatulence, which can interfere with its continuous administration. However, we still do not clearly know how long this side effect continues for the administration of acarbose despite several previous reports about this unpleasant adverse reaction. A major reason why its duration was obscure in such studies was that its duration was not accurately evaluated due to the fact that all subjects were ambulatory patients. Therefore, we monitored the daily flatulence among 48 diabetic inpatients treated with acarbose. As a result, we clarified that this system continues for a shorter period (12.8±1.3 days) than reported in previous studies. In addition, we found that obese patients are very frequently complicated with increased flatulence after taking acarbose since the BMI was significantly higher in the increased flatulence group than in the non-increased flatulence group with acarbose (25.1±0.7 vs 22.3±0.9).

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Poly (DL-lactic acid), irinotecan and polyethylene glycol monostearate were dissolved in acetone, and copre-cipitated by the addition of water. Then, the organic solvent was evaporated. The nanoparticle-containing suspension (NP-S) obtained by that coprecipitation was characterized both in vitro and in vivo. The nanoparticles showed a mean diameter of 150nm with its distribution of 110 to 270nm. At least 20% (w / w) of the drug was incorporated in the nanoparticles. These particle characteristics of NP-S were reproducibly obtained. When the antitumor effect was examined by the i.v. administration at repeated doses of 20mg irinotecan eq. / kg / day for 3 days (20×3 mg irinotecan eq. / kg) using mice bearing sarcoma 180 subcutaneously, NP-S was found to be sig-nificantly effective and it also tended to show a better suppression of tumor growth than an irinotecan hydrochloride (CPT-11) aqueous solution. After i.v. injections in rats, NP-S retained the plasma concentration of irinotecan longer than a CPT-11 aqueous solution. These findings suggest that NP-S may possibly improve the action of irinotecan against solid tumors.

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A new way of administrating metformin has been reviewed for the treatment of diabetic patients suffering from obesity and insulin resistance.
We studied the effectiveness of the combined administration of metformin and insulin in diabetic patients who were severely or slightly obese. These patients were selected from a group of inpatients and outpatients at Tokyo Metropolitan Futyu Hospital during the period from April 1999 to January 2001. We included 37 patients who were obese and who possibly demonstrated insulin resistance, and who also had problems controlling their blood glucose level despite insulin treatment. Patients were excluded if they were diagnosed to have either a hepatic or renal dysfunction or either cardiovascular or any circulatory disorders since they are risk factors for lactic acidosis after the administration of metformin.
After evaluation of the results of the combined administration of metformin and insulin, and also controlling the blood glucose level, and by varying the dosages of insulin, an improvement in the control of the blood glucose level was observed in 30 patients, and a reduction in the dosage of insulin was observed in 11 patients. No side effects which required a discontinuation of medications were discovered during the study period.
The previously reported administration ranged from 850-2, 500mg/day in the U.S. and Europe. In addition to the combination use of 500mg-750mg/day of metformin with insulin was also found to be effective. Based on these results, we believe that further clinical studies with a larger number of patients are called for to evaluate the optimal administration dosage of metformin.

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Pancreatic cancer is one of the most resistant malignancies and operations, radiotherapy and chemotherapy have all been widely used for the treatment of this disease. Gemcitabine, a new drug against pancreatic cancer, has been accepted for use in a palliative setting in Japan since April 2001. It is highly important for pharmacists to check for adverse effects of new drugs, especially in the case of chemotherapeutic agents, because these agents may exhibit many serious adverse effects such as hematologic toxicity that could be fatal to patients.
In this study, we investigated the adverse effects of gemcitabine to improve the pharmaceutical care of patients with pancreatic cancer. In a survey of adverse effects, severe leukopenia was observed in most patients. G-CSF (granulocyte colony-stimulating factor) has been commonly used as a therapeutic agent for leukopenia, and its major principal action is to stimulate the proliferation, differentiation, and function of the granulocyte lineage in the peripheral blood. Another action is to cause marrow stem cells to migrate into the peripheral blood. Because of this latter action, it is advised that G-CSF should not be given concurrently with chemotherapeutic agents, and should be discontinued at least 24 hours before and after the administration of chemotherapeutic agents. Since there have been some patients in whom G-CSF was administered within 24 hors of gemcitabine treatment, we provided drug information about the optimal usage of G-CSF to doctors concerned. As a result, a normal level of leukocytes could be maintained, and the usage of G-CSF was decreased.
In conclusion, we confirmed that leukopenia is the major adverse effect of gemcitabine in pancreatic cancer patients, and demonstrated that the appropriate use of G-CSF for the treatment of gemcitabine-induced leukopenia makes this chemotherapy both safer and more economical.

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The effects of four dihydropyridine calcium antagonists (manidipine, benidipine, amlodipine and nitrendipine) on the plasma digoxin level and the renal hemodynamics were studied in both patients and conscious normotensive beagle dogs.
In the clinical study, the combined administration of digoxin with calcium antagonists elevated, plasma digoxin levels compared with digoxin monotherapy, however, the difference was not significant. In dogs, the combined administration of digoxin with benidipine or nitrendipine resulted in a significantly higher plasma digoxin level after 8 and 24 hrs, respectively, but it did not affect the mean area under the plasma digoxin concentration time curve.
In a renal hemodynamic study in dogs, the glomerular filtration rate was observed to decrease significantly following the combined administration with manidipine. Furthermore, the filtration fraction decreased significantly after the administration of manidipine and benidipine, but it did not affect the renal plasma flow. In addition, amlodipine slightly decreased the glomerular filtration rate. On the other hand, nitrendipine did not alter the renal hemodynamics.
Since dihydropyridine calcium antagonists demonstrate different effects on renal hemodynamics during the combined administration of digoxin, administering the appropriate dosage of digoxin during combined therapy with calcium antagonists is therefore necessary to minimize the risk of digoxin toxicity.

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