Pharmacokinetics quinidine

Russo ME, Russo J, SmithRA, Pershing LK. The effect of phenytoin on quinidine pharmacokinetics, Drug Intell Clin Pharm (1982) 16, 480. 

In an open study, 6 healthy subjects were given a single 200-mg dose of quinidine sulfate before and on day 5 of a 6-day course of disulfiram 200 mg daily. There were no changes in quinidine pharmacokinetics during disulfiram administration. Disulfiram is thought to be an inhibitor of the cytochrome P450 isoenzyme CYP2E1, but this isoenzyme does not... 

Stanford RH, Park JM, Geraets Dr, Min DI, Lee H-C. Effect of oral erythromycin on quinidine pharmacokinetics in healthy volunteers. Pharmacotherapy (1998) 18,426-7. 

Kessler KIs4 Humphries WC, Black M, Spiarm JF. Quinidine pharmacokinetics in patients with cinhosis or receivii prcpianolol. Am Heart J (1978) 96,627-35. 

Besides catalyzing styrene and benzaldehyde, CYP enzymes play an important role in the metabolism of endogenous compounds as well as in pharmacokinetics and toxicokinetics. Joseph [228] developed a biosensor with human CYP3A4 as a novel drugscreening tool. It was constructed by assembling enzyme films on Au electrodes by alternate adsorption of a layer of CYP3A4 on top of a layer of PDDA. The biosensor was applied to detect verapamil, midazolam, quinidine, and progesterone. 

Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999 48(6) 829-838. 

Antipsychotics produce more important pharmacodynamic than pharmacokinetic interactions because of their multiple effects. Additive effects may occur when these drugs are combined with others that have sedative effects, a-adrenoceptor-blocking action, anticholinergic effects, and—for thioridazine and ziprasidone—quinidine-like action. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

Pope LE, Khalil MH, Berg JE, et al. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J Clin Pharmacol 2004 44 1132-1142. 

Pedersen KE. Digoxin interactions. The influence of quinidine and verapamil on the pharmacokinetics and receptor binding of digitalis glycosides. Acta Med Scand Suppl 1985 697 1-40. 

Pharmacokinetics Quinidine sulfate is rapidly and almost completely absorbed after oral administration. 

After single oral doses of 4.5 mg/kg of quinidine sulphate to 10 subjects, peak plasma concentrations of 0.9 to 1.8 xg/ml (mean 1.2) were attained in about 50 minutes (T. W. Guentert et al., J. Pharmacokinet. Biopharm., 1979, 7,315-330). 

Hager WD, Fenster P, Mayersohn M, Perrier D, Graves P, Marcus FI, Goldman S. Digoxin-quinidine interaction Pharmacokinetic evaluation. N Engl J Med 1979 300 1238-41. 

Pharmacokinetics. Absorption of quinidine from the gut is rapid, 75% of the drug is metabolised and the remainder is eliminated unchanged in the urine (t/ 7 h). Active metabolites may accumulate when renal function is impaired. 

Davidian, M. Gallant, A.R. Smooth non-parametric maximum likelihood estimation for population pharmacokinetics, with application to quinidine. J. Pharmacokinet. Biopharm. 1992, 20, 529-556. 

The pharmacokinetic interaction of quinidine with digoxin also occurs with quinine (280,281) and hydroxychloroquine (282). However, the effects of these drugs are smaller than those with quinidine. Quinine reduces the extrarenal clearance of digoxin, perhaps by altering its biliary secretion (283). 

Doering W. Quinidine-digoxin interaction Pharmacokinetics, underlying mechanism and clinical implications. N Engl J Med 1979 301(8) 400. ... 

Fenster PE, Powell JR, Graves PE, Conrad KA, Hager WD, Goldman S, Marcus FI. Digitoxin-quinidine interaction pharmacokinetic evaluation. Ann Intern Med 1980 93(5) 698-701. 

Kuhlmann J, Dohrmann M, Marcin S. Effects of quinidine on pharmacokinetics and pharmacodynamics of digitoxin achieving steady-state conditions. Clin Pharmacol Ther 1986 39(3) 288-94. 

The pharmacokinetic interaction of quinidine with digoxin also occurs with quinine and hydroxychloroquine (49). 

In vitro studies have suggested that the oxidation of quinidine to 3-hydroxyquinidine is a specific marker reaction for CYP3A4 activity. In six healthy young men the pharmacokinetics of a single oral dose of quinidine 200 mg were studied before and during daily administration of itraconazole 100 mg (106). Itraconazole reduced quinidine total clearance, partial clearance by 3-hydroxy-lation, and partial clearance by A-oxidation by 61, 84, and 73% respectively. 

Cooke CE, Sklar GE, Nappi JM. Possible pharmacokinetic interaction with quinidine ciprofloxacin or metronidazole Ann-Pharmacother 1996 30(4) 364-6. 

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