Population pharmacokinetics of quinidine
| Autor: | M. Borner, K. Fattinger, H. R. Ha, F. Follath, S. Vozeh |
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| Rok vydání: | 1991 |
| Předmět: |
Adult
Male Quinidine Population Renal function Pharmacology Models Biological Liver Function Tests Pharmacokinetics Oral administration medicine Humans Computer Simulation Pharmacology (medical) education Aged Aged 80 and over Heart Failure Volume of distribution education.field_of_study business.industry Maintenance dose Liver Diseases Body Weight Middle Aged Bioavailability Regression Analysis Female business Monte Carlo Method Research Article medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 31:279-286 |
| ISSN: | 0306-5251 |
| DOI: | 10.1111/j.1365-2125.1991.tb05531.x |
| Popis: | 1. Population pharmacokinetic parameters of quinidine were determined based on 260 serum drug concentration measurements in 60 patients treated for arrhythmias with quinidine sulphate or quinidine bisulphate (Kinidin duriles) orally. 2. Quinidine kinetics were best described by a two compartment model with zero order absorption from the gastrointestinal tract. The pharmacokinetics are influenced by severe heart or liver failure and renal function impairment. No effect was found for mild or moderate heart failure, for age, for body weight or for coadministration of nifedipine. 3. Population pharmacokinetic parameters of quinidine (assuming 100% bioavailability of oral quinidine sulphate) were: nonrenal clearance for patients without severe heart and liver failure 12.6 l h-1, reduction in patients with severe heart or liver failure to 6.8 l h-1, renal clearance (l h-1) related to creatinine clearance (ml min-1), proportionality constant 0.0566, volume of distribution of the central compartment 161 l, maximum serum drug concentration 1.4 h after administration of quinidine sulphate and 6.0 h after administration of quinidine bisulphate. 4. The results were validated by predicting the serum drug concentration in a separate group of 30 patients. The model reliably predicted both the population average and the variability of the serum concentration of quinidine. 5. Using Monte Carlo computer simulations, an a priori dosing regimen was derived that should maximize the proportion of patients having quinidine serum concentrations within the recommended range (2-5 mg l-1): initial dose of 600 mg quinidine sulphate in all patients, 3 h later first maintenance dose of quinidine bisulphate.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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