Monitoring the area under the concentration-time curve (AUC) of drugs has been advocated for therapeutic drug monitoring (TDM) as a means of making adjustments to achieve the optimal dose. However, conventional methods of measuring AUC require many blood samples to be taken after administering the drug, which is not viable in clinical practice. In this study, AUC monitoring was adapted to TDM for HIV protease inhibitors (PI) in HIV-infected patients, by designing equations for estimating the AUC using a small number of blood samples. In multiple regression analysis using cumulative PI plasma data from HIV-infected patients, it was found that trough levels (C0) could not explain the variation in their AUC values. In patients treated with ritonavir (RTV) plus indinavir (IDV), the optimum and minimum sampling time points for estimating the AUC of IDV were C0and C2 (R2=0.904). In patients treated with RTV plus saquinavir (SQV), the optimum and minimum sampling time points for both drugs were C0and C4 (R2=0.957, 0.967, respectively). In patients treated with Kaletra (combination of RTV and lopinavir (LPV)), the contribution of plasma LPV to the AUC of LPV at any sampling time was very small. However, the plasma concentration of RTV correlated well with the AUC of LPV, and the optimum and minimum sampling time points for estimating the AUC of LPV were C0and C6for LPV and C6for RTV (R2=0.904). These results suggest that our equations could be used successfully for estimating the AUC of PIs in clinical practice from a small number of samples.
A pharmacokinetic analysis program (MULTI-Win) based on the nonlinear least squares method available in Microsoft Windows XP was developed for use in clinical practice. Using the free software, Discoversoft Active Basic, MULTI-Win was constructed by altering the MULTI program written in BASIC language included in the Windows XP operating system. This program supports clinically essential pharmacokinetic equations, which can be altered by the user, estimates drug pharmacokinetic parameters and simultaneously fits curves to observed time courses. It is also easy to operate the program on microcomputers running on Windows XP. When MULTI-Win was executed for the time course of propofol in a threecompartment model with continuous infusion, a few minutes was required to achieve accuracy and stability in the calculation. Our findings indicated that MULTI-Win would be useful in therapeutic drug monitoring for achieving a quick response in dosage adjustments for individual patients, and be helpful overall in the daily work of the clinical pharmacist.
It is important for the clinical pharmacist to maintain the safety and efficacy of drug therapy for individual patients. In order to improve prescribing and help patients to understand their medication better, we began checking prescriptions and providing medicines to patients individually in the oncology surgery ward of our hospital in January 2003. Before preparing medications, we investigated the compliance of each patient through counseling, checked their prescriptions, and pointed out prescription errors to physicians. On the following day, after filling the prescriptions, we handed them to individual patients and explained the medication to each patient. Half a year after introducing this system, we calculated pharmacist prescription intervention rates and analyzed the results. We found a 49% error rate in prescriptions and pointed out the errors to physicians, 93% of which they acknowledged. To evaluate our system, we conducted a questionnaire survey of the doctors and nurses in the oncology surgery ward on the provision of medication by clinical pharmacists. We obtained a 95% response rate and the results were very satisfactory. The checking of prescriptions by clinical pharmacists in this ward reduced inappropriate ordering of medicines, as well as the time taken for us to dispense them and that taken for nurses to distribute the medicines and instruct patients on how to take them. Providing medicines directly to patients enabled us to practice patient counseling more closely and helped ensure that they were taken properly.
Thirteen patients under an intensified regimen in which regular insulin was being administered 3-4-times a day were selected for our study. In order to improve both postprandial glucose control and QOL for these patients, the regular insulin was changed to rapid-acting human insulin analogues. Self-monitoring of blood glucose (SMBG) was conducted and glycosylated hemoglobin A (1C) (HbA1c), rate of hypoglycemic episodes, and body mass index were also monitored. In our role of pharmacist/Certified Diabetes Educator, wead-justed the doses in accordance with patient symptoms under the guidance of their doctors. Patients' comments were obtained and from them, their sense of unease before and after the change was investigated. Pharmaceutical care, nutrition control, and counseling were carried out on the basis of the results in order to keep the patients in an appropriate state in accordance with their symptoms. Regardless of variation in insulin doses, their QoL improved and incidence of hypoglycemia decreased. Patient autonomy and compliance were also enhanced.
Owing to the approval of reimbursement of fees for antineoplastic chemotherapy on an outpatient basis by the national health insurance scheme in April 2002, an antineoplastic chemotherapy room was set up in the ambulatory area of our hospital in August 2000. In order to ensure the effective use of the safety cabinet and other existing equipment and the safe administration of antineoplastic agents to patients, the authors assigned a mixing pharmacist and a coordinating pharmacist who was to be in charge of antineoplastic chemotherapy for outpatients. First, the mixing pharmacist prepared IV mixtures of the antineoplastic agents and auxiliary medicines in a sterile area and then the coordinating pharmacist audited the mixtures and carried them to the antineoplastic chemotherapy room. Other functions of the coordinating pharmacist included providing pharmaceutical care to patients and cooperating with doctors, nurses and other pharmacists involved in the chemotherapy. They also searched for information on individual medical charts or in patient statements and pointed out doubtful records or potential problems that might affect chemotherapy. Coordinating pharmacists notified 50 potential problems between August 2002 and April 2003. To evaluate our pharmaceutical practices in outpatient antineoplastic chemotherapy, we conducted a questionnaire survey of the patients. Their responses indicated that our pharmaceutical care program was working well and that they hoped we would continue it. However, the usefulness of our program was not entirely clear to all patients and we recognized the need to better inform patients concerning this.
The development of risk factors, such as obesity, for lifestyle-related vascular disease is heterogeneous. In this regard, recent studies have shown that mutation of the β3-adrenoceptor gene, involving replacement of tryptophan by arginine at position 64 (Trp 64 Arg) of encoding amino acid residues (obesity gene), was associated with increased susceptibility to obesity and insulin resistance, and affected obesity treatment in humans. In the present study, we tested for the presence of the obesity gene and examined its influence on pharmacotherapy for lifestyle-related vascular disease. Our study investigated 92 persons receiving medication (depressors, lipid-lowering drugs, oral agents for diabetes; medication group) for a lifestyle-related illness among 2453 persons who consented to β3-adrenoceptor gene determination. There was no difference in the prevalence of the obesity gene between those receiving medicine and those not receiving any. In the medication group, there were no significant differences in the average T-C, TG, LDL-C, RLP-C, glucose, HbAic and BMI measurements among subjects who had the obesity gene. Also, when the minimal cholesterol target following therapy was set to 220 mg or less, this was achieved in all subjects without the obesity gene (wild group). In subjects with the obesity gene, there were many cases in which RLP-C was over 8 mg/dL. These results suggest that the obesity gene would enhance resistance to pharmacotherapy intended to improve lipid levels in the treatment of lifestyle-related vascular disease.
To determine the influence of the angle of holding an eye medication container on the squeezing force needed for each drop of the medication and drop volume, we measured squeezing force and drop weight using a force gauge for 11 prod ucts commercially available in Japan, at 3 different angles to the horizontal surface-90°, 60° and 45°. At 90°, the squeezing force for each drop varied from 0.770kg (Tobracin®) to 1.575kg (Timoptol® 0.25%) and at 60° and 45°, the squeezing force decreased for all products except KetasR. Thus the squeezing force was affected by the angle of holding the container. At 90°, drop weight varied from 33mg (Ketas®) to 44mg (Tobracin®). At 60° and 45°, drop weight decreased for all products except Hyalein® 0.1, Kary Uni® and Sanpilo® 2% (tip and cap type). These results show that the angle of holding an eye medication container is an important factor because of the influence it has on drop size and squeezing force. For this reason, the optimal angle for patients to hold eye medication containers should be investigated in greater depth.
Labeling on the packages of over-the-counter (OTC) drugs contains very important information to help consumers select and use them safely and effectively. In the present study, we investigated the differences in drug information and risk management given for OTC nasal decongestants and sprays between the United States and Japan. The American products had the new standardized Drug Facts label demanded by the Food and Drug Administration, but there was still no standardized label in Japan. The Drug Facts list the active ingredients, uses, warnings, inactive ingredients, purpose, and directions. They use plain language so that consumers may easily understand the benefits and risks. There were “Specific Warnings” consisting of one telling people under what circumstances they should consult a doctor or pharmacist, a pregnancy/nursing warning, and those concerning accidental overdose and side effects. For the Japanese labeling, “Precaution” was used instead of “Warning”, and there were no specific precautions. While age limits were given on all of the American labeling to prevent overdosing in infants, some of the Japanese labels did not provide such information. In addition, the American labeling included emergency contact numbers that consumers could phone in case of accidents. There were 65 poison control centers, which could be called 24 hours a day toll-free. In contrast, numbers were only given for 2 such centers in Japan, and they were not toll-free, deterring wide use due to the cost involved. We found many differences in the labeling of OTC nasal decongestants and sprays between the U.S. and Japan, which would depend on consumers' rights and product liability. The results of this study suggest that OTC drug labeling in Japan must be improved and a standardized format established for this purpose.
Arsenic trioxide (As2O3) chemotherapy is now used for the treatment of relapsed patients with acute promyelocytic leukemia (APL) and adult T-cell leukemia (ATL) in the First Internal Medicine Department of Fukuoka University Hospital. In order to adjust the dosage, we studied the pharmacokinetics of As2O3 when administered intravenously to patients with APL and ATL. Plasma arsenic concentrations were measured by gas-chromatograph/mass-spectrometry (GC/MS). The maximum arsenic concentration (Cmax) and area under the curve (AUC) were 8.3±0.8 (μM) and 61.7±4.2 (μM·hr) on the first day and 8.6±0.7 (μM) and 63.5±6.6 (μM·hr) on the twentieth day of treatment, respectively. Apparent distribution volume and total body clearance were 0.14±0.02 (L/kg) (range 0.12-0.18) and 0.036±0.004 (L/hr/kg) (range 0.030-0.039), respectively. From these results, we conclude that the pharmacokinetic behavior of As2O3 did not alter in continuous administration, and the variation in pharmacokinetic parameters was extremely small among the patients.