The population pharmacokinetic parameters of valproic acid in pediatric patients taking tablets (Depakene^® R) which were designed to be long acting were estimated using the standard two-stage method. On this study, the patients comprised seven pediatric outpatients of our hospital, aged 8 to 12 years old, all of whom were in the steady-state level. Blood samples were collected just before administration and six times thereafter until 30 h. The pharmacokinetic parameters were calculated by utilizing a one-compartment model with first-order absorption after a lag time by using the Phaconet-Depakene^® program.
Although the estimated population pharmacokinetic parameters, apparent elimination rate constant (Ke, h^-1), apparent volume of distribution (Vd, 1/kg) and apparent absorption lag time (Lag, h) of pediatric patients did not differ from those of adult healthy volunteers reported previously, apparent absorption rate constant (Ka, h^-1) was significantly smaller than that of adults. Prediction of the maximum and minimum concentration with the Bayesian method using these estimated parameters and one-point serum concentration data showed that the prediction error was less than 10%. At the steady state, the concentration of serum valproic acid decreased until 2.9h after administration. It is noteworthy important that the esrum concentration level about 3 hours after administration of Depakene^® R did not indicate the maximum concentration but rather the minimum concentration.
In conclusion, the estimated population pharmacokinetic parameters of valproic acid in pediatric patients taking Depakene^® R were determined for the Bayesian analysis by Phaconet-Depakene^®.

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Improvement of povidone-iodine sugar (PI) formulation which is used for treatment of decubitus and wound was attempted. Three model formulations and the existing hospital preparation (IS) were compared with respect to characteristics, pH, osmotic pressure, hardness and effective iodine. When PIs were kept at room temperature without light for 14 days, the hardness of each increased. It was found that osmotic pressure and hardness could be controlled by the addition of glycerin. An optimum formulation of PI containing glycerin (IGS) was chosen based on the restriction of hardness and osmotic pressure. The usefulness of IGS was compared with IS through a questionnaire sent to doctors and pharmacists. As a result, the clinical effect of IGS was the same as IS, but the usefulness, spreadability and sensitivity on use of the former were superior to those of IS.

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The change in rat serum, brain and cerebrospinal fluid (CSF) concentration-time profiles, and serum protein binding of nalidixic acid (NA) caused by fenbufen was studied.
Periodically following the bolus i.v. administration of NA (10 mg/kg) alone or with fenbufen (20 mg/kg) to 10-week old male Wistar rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the rat sacrificed by microwave irradiation. Serum (total and unbound), brain and CSF levels for the drug were determined by HPLC method.
Serum levels for NA declined mono-exponentially with time in both groups, and coadministered fenbufen caused a significant duration in the serum level for the quinolone. The fraction of NA bound to serum protein was hardly affected by fenbufen. In both groups, brain and CSF levels for NA rose quite rapidly after drug administration and then declined along with the serum levels. Even in the group given NA alone, both brain and CSF levels for the quinolone were considerably high, yielding approximately 1.4 and 1.1 as the ratio to the serum unbound levels, respectively. Fenbufen was found to increase these brain and CSF concentrations significantly to exactly the same extent as observed in serum levels, showing no change in the ratio of brain (about 1.4) or CSF (about 1.1) concentration to serum unbound concentration for NA from the ratio obtained for NA alone.
These results indicate that the duration of the brain or CSF level for NA in the coadministered group was merely due to the increase in the serum level for NA and that fenbufen did not affect the permeability of NA into the CNS.

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Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) can serve as a significant source of MRSA infection in patients. Ethacridine (acrinol, ACR) and methylrosanilium chloride (pyoktanin, PYO) present antimicrobial activity against gram-positive bacteria and therefore are clinically used as topical disinfectants. The purpose of the present study was to evaluate the in vitro antimicrobial activity of ACR and PYO against MRSA, in order to ascertain whether or not ointments of ACR and PYO are applicable to the eliminatation of MRSA from the anterior nares. Minimal inhibitory concentrations (MICs) of ACR and PYO for 100% of MRSA isolates were 400 μg/ml and 0.5 μg/ml, respectively. Clinical isolates of MRSA were killed within 10 min at 20°C after exposure to 1% ACR, 0.01% PYO and 0.1% PYO, while no bactericidal effect of 0.1% ACR was observed after 24-h exposure. The logarithmic reduction factors of 0.01% and 0.1% PYO for an MRSA isolate after 60-min exposure at 30°C were over 4. All of the 0.01% PYO ointments prepared with three different bases showed antimicrobial activities against the MRSA isolate tested. The MIC₁₀₀ of PYO ointment prepared with hydrophilic plastibase for MRSA was 100 μg/g. These results suggest that PYO oitment is applicable for topical use to eradicate nasal carriage of MRSA.

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Zonisamide (ZNS) is a useful anticonvulsant, but its pharmacokinetic properties are not sufficiently known. We discuss the optimal dosage regimen for ZNS by means of therapeutic drug monitoring (TDM). In our examination of whether the coadministration of other anticonvulsants might affect the serum concentration of ZNS, the following results were obtained: 1) a higher dosage of ZNS was required for the patients under 13 years old than for elderly patients to maintain the similar serum ZNS levels; 2) the serum protein binding rate of ZN.S was less than 40%, indicating serum levels of ZNS might unlikely be affected by coadministration of other protein-binding agents, although when ZNS was administered with valproic acid (VPA), both the binding rates of ZNS and VPA tended to decrease; 3) the serum concentrations linearly correlated with the doses when 10 mg/kg or less was given; 4) the serum ZNS concentration tended to decrease with coadministration of other anticonvulsants such as phenytoin, carbamazepine and phenobarbital, which are known to induce hepatic microsomal enzyme systems; and 5) thus TDM provides useful information on the appropriate dosage adjustments for ZNS.

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When sustained release preparations, featuring a pH-dependent dissolution, are used concomitantly with medication containing antacids, the possibility exists of adverse effects being generated on the sustained release action.
We thus studied the dissolution of nifedipine when sustained-release nifedipine granules (KB-1712P) were administered concomitantly with widely used antacids, using a modified Fuchs method which simulated the mechanism in the body.
The results showed that the dissolution rate of nifedipine tended to increase when it was administered concomitantly with sodium bicarbonate or Maalox^® with a neutralization endpoint in a 0.1N-HC1 at a pH of at least 6. However, no effects on the dissolution rate were seen when SM-Powder^® with a low content of sodium bicarbonate or Kolantyl Granules^® exhibiting with a neutralization endpoint at pH 4 was administered. These results suggest that it is necessary to administer sodium bicarbonate or Maalox^® at different times when they are used concomitantly with sustained-release nifedipine granules.

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The microbial contaminations of inhalant preparations, in which 2% orciprenalin sulfate solution and 0.2% bromhexine hydrocloride solution were mixed with sterile physiological saline (Prescription 1) and 0.125% tyloxapol solution was mixed with sterile physiological saline (Prescription 2), were investigated using two types of bottles on non-medical staffs assumed to be outpatients using inhalant preparations. As a result, each sample of Prescription 1, to which were added preservatives, was not contaminated either at room temperature under light protection or at a cool temperature under light protection. On the other hand, some samples of Prescription 2, which had no preservatives added, were contaminated with Pseudomonas sp., Flavobacterium sp. and Bacillus sp. over 10² CFU/ml. Accordingly, it was found that inhalant preparations cannot be prevented from microbial contamination without preservatives regardless of storage conditions and bottle types. Therefore, preservatives should be added to inhalant preparations to ensure their safe use without contamination.

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Three kinds of activated charcoal suspensions using a laxative solution as a dispersion medium were prepared to provide for acute intoxication. Used in the dispersion medium were 13.6% magnesium citrate, 15.0% magnesium sulfate and 75.0% D-sorbitol. These suspensions and a suspension using an isotonic sodium chloride solution as a dispersion medium (control) were sterilized for the purpose of long-term storage.
The adsorption power was tested by a modified adspoption test of the JP XII medicinal carbon and a modified one of the USP XXII activated charcoal. The suspensions of magnesium citrate and D-sorbitol failed in the methylene-blue adsorption test of JP XII. The other suspensions passed every adsorption test. The adsorption power of the suspensions for phenobarbital, which is often responsible for drug poisoning, was estimated to be ca. 300 mg drug per gram of charcoal, and was stable over two months at room temperature. After 30 months of storage, the adsorption power decreased to 92% of its initial value while the magnesium sulfate suspension observed a reduction of 40%.
We conclude that these suspensions are suitable activated charcoal formulations for provision to the emergency room due to the adsorption power and stability.

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We tried to improve buprenorphine (BN) sublingual tablets (previous tablets) prepared previously [Yakuzaigaku, 46: 134-139 (1986)] by focusing on shortening the disintegration time because the disintegration of these tablets sublingually in man is quite long (7-9 minutes). Five different tablets (100mg) containing 100μg of BN were prepared, and the qualitative characteristics, pharmacokinetic behavior and clinical effect of BN were compared with the previous tablets. In the quality tests, one of the new tablets comprising 78.1 mg of 0.128% BN powder, 19.9 mg of lactose, 1 mg of magnesium stearate and 1 mg of powdered acacia per tablet was superior to the other products in terms of both disintegration and dissolution. The mean sublingual disintegration times fos the placebo of the new tablet in five healthy volunteers and five patients were 3.0 and 3.6 minutes, respectively, values which were significantly shorter than those (7.5 and 6.5 minutes) for the previous tablet. The plasma concentration of BN or analgesic effect arising after sublingual administratation of the new tablet in one healthy volunteer and two patients were closely comparable with those following sublingual administration of the previous tablet. The new tablet is biologically and pharmacologically equivalent to the previous one and is superior to the previous tablet in terms of disintegration characteristics.

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The amount of [6]-Shogaol (6-S) and [6]-Gingerol (6-G) in varions kinds of commercially available Shosaiko-To was determined by HPLC. There were three differences observed in 6-S and 6-G in Shosaiko-To preparations. First, one Shosaiko-To preparation contained tenfold as much of the total amounts of 6-S and 6-G as did the other preparations. Second, one preparation embodied fiftyfold as much 6-S as did the other preparations. Finally, one preparation comprised elevenfold as much 6-G as did the other prepartions.

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In a small local hospital, we have been positively trying to establish firmly our activity as clinical pharmacists. Our objectives have focused on two points: the one was managing with limitted manpower, and the other was keeping as long time as possible for interviewing inpatients. The past prescription records for inpatients were modified and used as medication histories, when inpatients were given mediational instructions. Our research revealed that the time it took to complete the medication histories was reduced, and our clinical pharmacy activity could be introduced to our hospital as a routine job without requiring any additional manpower. Also much longer time could be allocated to interviewing inpatients, making possible more efficient medicational instructions.

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We have constructed an in-house database by using a method that employs the commercial application software called “The CARD” . This was done after modifying the formulary data using the word processor program “Ichitaro” . The derived database offers selected information which permits the retrieval of such specifics as drug names, dosages, indications, contraindications, adverse reactions, drug interactions, and precautions.

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