Fujio Nakagawa

Estimation of plasma unbound phenobarbital concentration by using mixed saliva.

Summary: Relationships among plasma total (Ct), plasma protein unbound (Cf) and mixed salivary (Cs) concentrations of phenobarbital (PB) were studied in 29 epileptic patients. A highly significant correlation was observed between C, and Cf. Although a significant correlation was observed between Cf and Cs, Cs/Cf ratio was only 0.63. When Cs was corrected by using pKa (7.41) and pH of saliva to estimate free PB concentration (Cest f), a highly significant correlation was obtained between Cf and Cestf, and Cest f/Cf ratio was 0.96. The temporal course of Cest f obtained from Cs after an oral single dose of 50 mg PB in a healthy adult male volunteer was approximated as a triexponential equation. The peak time was 2 hr after ingestion and apparent half‐life was 66 hr. The prediction of minimum concentrations at steady state on the basis of these parameters corresponded well with actually obtained Cest f following repetitive administration of PB.

Quantitative determination of furosemide in plasma, plasma water, urine and ascites fluid by high-performance liquid chromatography

A high-performance liquid chromatographic method using spectrofluorometric detection is described for the determination of furosemide in plasma, plasma water, urine and ascites fluid. The extraction procedure decreases interference from endogenous substances. The detection limit of furosemide is 10 ng in 0.5 ml of biological sample. The method is sufficiently sensitive for pharmacokinetic study of furosemide with normal subjects and patients with liver cirrhosis and/or renal disease after oral administration of furosemide in a retard capsule, and for study of protein binding of furosemide in patients with various diseases.

Determination of pemoline in plasma, plasma water, mixed saliva, and urine by high-performance liquid chromatography.

Summary A new determination method of pemoline in plasma, plasma water, mixed saliva, and urine using high-performance liquid chromatography was developed. The detection limit of pemoline using 0.2 ml of the sample was 0.02 μg/ml in plasma, plasma water, saliva, and urine. The recoveries of pemoline added to plasma, saliva, and urine (each 6 μg/ml) were more than 98%. The coefficients of variation of within-run and between-run precisions for 5 concentrations of pemoline in plasma were less than 5 and 6%, respectively. The elimination half-lives of pemoline obtained from the plasma concentration-time curves after a single oral administration of pemoline in two subjects were 6.7 and 10.3 h. Mean values of the ratio between saliva and plasma total concentration in two subjects were 0.55 and 0.64, and mean values of plasma protein binding percent were 35.7 and 25.2%, respectively. The saliva concentrations were in proportion to the plasma unbound pemoline concentrations at simultaneous samplings, and the ratios between saliva and plasma unbound concentration were about 0.9 in two subjects. Usefulness of saliva in the estimation of plasma protein-unbound pemoline concentration was noted.

Determination of ambenonium in biological samples by reversed-phase ion-pair liquid chromatography.

A sensitive and selective analytical method for the determination of ambenonium ion in biological samples is described. The procedure involves ion-pair extraction of the drug, followed by reversed-phase ion-pair chromatographic analysis with ultraviolet detection at 217 nm. The detection limits at a signal-to-noise ratio of 5 were 100 pmol/ml using 0.2 ml of plasma and bile, 250 pmol/ml using 0.2 ml of urine and 200 pmol/g using 1 ml of tissue homogenates containing 0.1 g/ml of each tissue. This assay procedure was used to study the pharmacokinetics of ambenonium ion after intravenous administration in rats.

Determination of pemoline in plasma, urine and tissues by reversed-phase high-performance liquid chromatography

A simple and selective high-performance liquid chromatographic method with ultraviolet detection at 215 nm for the determination for pemoline in rat plasma, urine and tissues is described. Pemoline in the samples was extracted with methylene chloride at pH 10 and the organic phase was evaporated after adding 5-methyl-5-phenylhydantoin used as an internal standard. Pemoline and the internal standard were separated on a Kaseisorb LC C8-60-5 reversed-phase column. The limits of determination of pemoline in 0.1-0.2 ml of plasma, urine and tissue homogenates were 2, 100 and 20 ng, respectively. The method should be useful for studies of the pharmacokinetics and distribution of pemoline in small animals.

Clinical Application of Immunoprecipitation Inhibition Technique for Determination of Carbamazepine and Theophylline in Serum

The immunoprecipitation inhibition technique (i-PiT method) was used in the clinical application to determine the concentration of carbamazepine (CBZ) and theophylline (TH) in serum. Each coefficient of variation for the 3 levels of CBZ or TH was less than 9% within-run and betweenrun. The serum CBZ concentration determined by the i-PiT method was compared with that determined by high-performance liquid chromatography (HPLC). The correlation coefficient was 0.990, but serum CBZ concentration determined by the i-PiT method was about 15% higher than that determined by HPLC because of the cross reactivity in carbamazepine-10, 11-epoxide. Other antiepileptic drugs, such as phenytoin, phenobarbital and primidone, did not interfere with the i-PiT method under therapeutic condition. The serum TH concentration determined by the i-PiT method was compared with that determined by HPLC. There was good agreement between the i-PiT method and HPLC results, where the correlation coefficient was 0.994. The metabolites of TH, such as caffeine and theobromine, did not interfere with the i-PiT method under therapeutic conditions. Therefore, the i-PiT method may be useful for the serum level monitoring of patients undergoing TH therapy.

Statistical Survey of Oral Drugs in Prescriptions at Hospital Pharmacy

A study was made on the number of oral drugs by dosage form and by specialty, drugs commonly used in specialties, frequency of prescribing and the number of drugs prescribed, comparison of the frequency, and other matters. The oral drugs were selected from prescriptions for inpatients staying in the hospital for 5 months. Five lists of date of prescription, names of specialties, names of drugs, quantity of drugs and period of administration (days) were made up by use of computers (TOSBAC-40 and TOSBAC-5400). Some significant findings were obtained in the study. But the subsequent study should be made in improved method and effective use of computers.