Urinary Excretion Kinetics of Intact Quinidine and 3-OH-quinidine After Oral Administration of a Single Oral Dose of Quinidine Gluconate in the Fasting and Non-fasting State

Overview

Journal Eur J Drug Metab Pharmacokinet

Date 1983 Oct 1

PMID 6673973

Authors

G Sirois

M A Gagnon

Affiliations

Soon will be listed here.

Abstract

To obtain more precise urinary excretion data of intact quinidine (D) and its main metabolite, 3-OH-quinidine (DM), the specific HPLC method of Bonora et al has been used to follow its urinary excretion kinetics. In a cross-over study, 2 commercial dosage forms of quinidine gluconate, fast- and slow-release, were administered to 18 healthy subjects who had fasted for 10 hours in 3 treatments which were administered during the fasting period (T1), and before (T2) of after (T3) a standard breakfast. The urine was collected at fixed time intervals for 72 hours after the administration of a single dose (405 mg of quinidine base). The difference between the drug release characteristics of the two products was studied by analysing the cumulative amount of D and DM excreted as a function of time, and the time required to reach the maximum value for the urinary excretion rate of intact quinidine. A food effect could be noticed among treatments with the conventional fast-release dosage form when comparing the maximum values of the urinary excretion rate of D (T2 greater than T1). There was no significant difference in the percentage of drug absorbed from the 2 products, according to the data on the cumulative amount of D and DM. The parameters estimated for quinidine and the metabolite were: the apparent half-life of elimination, the urinary excretion rates and the time to reach a maximum value in the urinary excretion rate. The urinary excretion rate constant and the renal clearance were also quantified for quinidine by combining urinary parameters with the corresponding serum data previously reported.

References

Spenard J, Sirois G, Gagnon M . Influence of food on the comparative bioavailability of a fast- and slow-release dosage form of quinidine gluconate. Int J Clin Pharmacol Ther Toxicol. 1983; 21(1):1-9. View

Drayer D, Hughes M, Lorenzo B, Reidenberg M . Prevalence of high (3S)-3-hydroxyquinidine/quinidine ratios in serum, and clearance of quinidine in cardiac patients with age. Clin Pharmacol Ther. 1980; 27(1):72-5. DOI: 10.1038/clpt.1980.11. View

Drayer D, Restivo K, Reidenberg M . Specific determination of quinidine and (3S)-3-hydroxyquinidine in human serum by high-pressure liquid chromatography. J Lab Clin Med. 1977; 90(5):816-22. View

Fieldman A, Beebe R, Sing Sum Chow M . The effect of quinidine sulfate on QRS duration and QT and systolic time intervals in man. J Clin Pharmacol. 1977; 17(2-3):134-9. DOI: 10.1002/j.1552-4604.1977.tb04600.x. View

Palmer K, Martin B, Baggett B, Wall M . The metabolic fate of orally administered quinidine gluconate in humans. Biochem Pharmacol. 1969; 18(8):8145-60. DOI: 10.1016/0006-2952(69)90280-9. View

Sirois G, Eshaque M, Chabot M . Relative bioavailability of three commercial quinidine dosage forms. Biopharm Drug Dispos. 1980; 1(4):167-77. DOI: 10.1002/bdd.2510010404. View

Ueda C, Williamson B, Dzindzio B . Absolute quinidine bioavailability. Clin Pharmacol Ther. 1976; 20(3):260-5. DOI: 10.1002/cpt1976203260. View

Guentert T, Daly J, RIEGELMAN S . Isolation, characterisation and synthesis of a new quinidine metabolite. Eur J Drug Metab Pharmacokinet. 1982; 7(1):31-8. DOI: 10.1007/BF03189540. View

Brodie B, Baer J, CRAIG L . Metabolic products of the cinchona alkaloids in human urine. J Biol Chem. 1951; 188(2):567-81. View

10.

Sirois G . Comparison of two spectrofluormetric procedures for quinidine determination in biological fluids. J Pharm Sci. 1977; 66(4):591-2. DOI: 10.1002/jps.2600660436. View

11.

Guentert T, Coates P, Upton R, Combs D, RIEGELMAN S . Determination of quinidine and its major metabolites by high-performance liquid chromatography. J Chromatogr. 1979; 162(1):59-70. DOI: 10.1016/s0378-4347(00)82063-0. View

12.

Guentert T, Holford N, Coates P, Upton R, RIEGELMAN S . Quinidine pharmacokinetics in man: choice of a disposition model and absolute bioavailability studies. J Pharmacokinet Biopharm. 1979; 7(4):315-30. DOI: 10.1007/BF01062532. View

13.

Conrad K, Molk B, Chidsey C . Pharmacokinetic studies of quinidine in patients with arrhythmias. Circulation. 1977; 55(1):1-7. View

14.

Drayer D, Lowenthal D, Restivo K, Schwartz A, Cook C, Reidenberg M . Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. Clin Pharmacol Ther. 1978; 24(1):31-9. DOI: 10.1002/cpt197824131. View

15.

Bonora M, Guentert T, Upton R, RIEGELMAN S . Determination of quinidine and metabolites in urine by reverse-phase high-pressure liquid chromatography. Clin Chim Acta. 1979; 91(3):277-84. DOI: 10.1016/0009-8981(79)90484-4. View

16.

Gerhardt R, Knouss R, THYRUM P, LUCHI R, MORRIS Jr J . Quinidine excretion in aciduria and alkaluria. Ann Intern Med. 1969; 71(5):927-33. DOI: 10.7326/0003-4819-71-5-927. View

17.

Chabot M, Sirois G . Bioavailability of three commercial sustained-release tablets of quinidine in maintenance therapy. J Pharm Sci. 1978; 67(10):1456-9. DOI: 10.1002/jps.2600671035. View

18.

Sirois G . NMR quantitative analysis of quinidine in mixtures of quinidine and hydroquinidine. J Pharm Sci. 1973; 62(8):1334-6. DOI: 10.1002/jps.2600620822. View

19.

Houston A, PERRY W . The plasma concentration of quinidine after oral administration and its effect on auricular fibrillation. Can Med Assoc J. 1950; 63(1):56-60. PMC: 1821684. View

20.

Sirois G . Importance of the purity control of commercial bulk quinidine and hydroquinidine salts. NMR analysis and apparent partition coefficients. Pharm Acta Helv. 1974; 49(1):37-40. View