Metabolism of quinine

Geiling, E. M. K.; Kelsey, F. E.

doi:10.1007/bf00244811

Cited by 4 publications

(5 citation statements)

References 2 publications

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Section: Discussionmentioning

confidence: 99%

“…This parameter, AUC(metabolite)/ AUC(unchanged drug), called metabolic ratio, is a known measure of extent of metabolism of a drug. Since quinine has a narrow therapeutic window [31], the fourfold increases in Cmax and AUCT of the drug by ritonavir would obviously be associated with toxic manifestations of quinine following therapeutic drug administration. A single 600-mg oral dose of quinine was used in this study so as to minimize adverse reactions that would result from the anticipated increased plasma concentrations of the drug with concurrent administration of ritonavir.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

Soyinka¹,

Onyeji²,

Omoruyi³

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Malaria is widespread across some areas of the world, most of which also bear the brunt of the human immunodeficiency virus (HIV) pandemic, resulting in a high incidence of co-infection of both diseases.• Ritonavir, a HIV protease inhibitor, and quinine, an antimalarial agent effective against multidrug-resistant Plasmodium falciparum, are likely to be administered concurrently for treatment of patients with HIV and malaria.• Both drugs are metabolized to a significant extent by CYP3A4 and ritonavir is a potent inhibitor of this enzyme. WHAT THIS STUDY ADDS• With increasing access to antiretroviral drugs, it is important that potential interactions between therapies for HIV and malaria infections are investigated.• In this study, concurrent administration of ritonavir with quinine was found to be associated with marked elevation in the plasma levels of the antimalarial and a pronounced decrease in plasma concentrations of 3-hydroxyquinine, the major metabolite of quinine.• There was also a modest but significant increase (P < 0.05) in plasma concentrations of ritonavir in the presence of quinine. AIMSTo evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers. METHODSTen healthy volunteers were each given 600-mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three-period pharmacokinetic nonrandomized sequential design study. Quinine was co-administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3-hydroxyquinine, using a validated high-performance liquid chromatography method. ) of the metabolite. Similarly, quinine caused modest but significant increases (P < 0.01) in the Cmax, AUC and elimination T1/2 of ritonavir. RESULTS Concurrent ritonavir administration resulted in about fourfold increases in both the CONCLUSIONSDownward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

Soyinka¹,

Onyeji²,

Omoruyi³

et al. 2010

Brit J Clinical Pharma

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“…The marked increase in the metabolic ratio of quinine further strengthens the point that a metabolic interaction occurs between quinine and nevirapine, and that nevirapine induces the metabolism of quinine. This raised level of 3‐HQN due to nevirapine co‐administration may reduce the efficacy of quinine as an antimalarial while simultaneously increasing toxicity, since 3‐HQN is reported to have a higher toxicity and a lower antimalarial activity than its parent compound 31 . Since quinine has a narrow therapeutic window, 31 the decrease in C max of up to 40% and 38% decrease in AUC of the drug in the presence of nevirapine are likely to be of clinical significance.…”

Section: Discussionmentioning

confidence: 99%

“…This raised level of 3‐HQN due to nevirapine co‐administration may reduce the efficacy of quinine as an antimalarial while simultaneously increasing toxicity, since 3‐HQN is reported to have a higher toxicity and a lower antimalarial activity than its parent compound 31 . Since quinine has a narrow therapeutic window, 31 the decrease in C max of up to 40% and 38% decrease in AUC of the drug in the presence of nevirapine are likely to be of clinical significance. Thus, adjustment of the quinine dose may be necessary when the drug is co‐administered with nevirapine.…”

Section: Discussionmentioning

confidence: 99%

Effects of concurrent administration of nevirapine on the disposition of quinine in healthy volunteers

Soyinka

Onyeji

Omoruyi

et al. 2009

Journal of Pharmacy and Pharmacology

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Objectives Nevirapine and quinine are likely to be administered concurrently in the treatment of patients with HIV and malaria. Both drugs are metabolised to a significant extent by cytochrome P450 (CYP)3A4 and nevirapine is also an inducer of this enzyme. This study therefore evaluated the effect of nevirapine on the pharmacokinetics of quinine. Methods Quinine (600 mg single dose) was administered either alone or with the 17th dose of nevirapine (200 mg every 12 h for 12 days) to 14 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analysed for quinine and its major metabolite, 3-hydroxquinine, using a validated HPLC method. Key findings Administration of quinine plus nevirapine resulted in significant decreases (P < 0.01) in the total area under the concentration–time curve (AUCT), maximum plasma concentration (Cmax) and terminal elimination half-life (T½β) of quinine compared with values with quinine dosing alone (AUC: 53.29 ± 4.01 vs 35.48 ± 2.01 h mg/l; Cmax: 2.83 ± 0.16 vs 1.81 ± 0.06 mg/l; T½β: 11.35 ± 0.72 vs 8.54 ± 0.76 h), while the oral plasma clearance markedly increased (11.32 ± 0.84 vs 16.97 ± 0.98 l/h). In the presence of nevirapine there was a pronounced increase in the ratio of AUC(metabolite)/AUC (unchanged drug) and highly significant increases in Cmax and AUC of the metabolite (P < 0.01). Conclusions Nevirapine significantly alters the pharmacokinetics of quinine. An increase in the dose of quinine may be necessary when the drug is co-administered with nevirapine.

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“…1,6 Quinine is mainly metabolized to its major metabolite, 3-hydroxyquinine (3-HQN), by cytochrome P450 (CYP) 3A4, whereas CYP 1A2 also plays a minor role in quinine biotransformation. 7,8 Antimicrobials are one of the most commonly prescribed classes of medications all over the world, 9 and these drugs are associated with many significant druginteraction activity as both inducers and inhibitors of enzymes. 10 Coexistence of malarial and bacterial infections is common in tropical regions, particularly in Africa.…”

Section: Introductionmentioning

confidence: 99%

Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration

Adegbola

Soyinka

Adeagbo³

et al. 2016

American Journal of Therapeutics

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This study evaluated the effects of concurrent ciprofloxacin administration on the disposition of quinine in healthy volunteers. Quinine (600-mg single dose) was administered either alone or with the 11th dose of ciprofloxacin (500 mg every 12 hours for 7 days) to 15 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analyzed for quinine and its major metabolite, 3-hydroxquinine, using a validated high-performance liquid chromatographic method. Administration of quinine plus ciprofloxacin resulted in significant increases (P < 0.05) in the total area under the concentration-time curve, maximum plasma concentration (Cmax), and terminal elimination half-life (T1/2b) of quinine compared with values with quinine dosing alone (AUC: 27.93 ± 8.04 vs. 41.62 ± 13.98 h·mg/L; Cmax: 1.37 ± 0.24 vs. 1.64 ± 0.38 mg/L; T1/2b: 16.28 ± 2.66 vs. 21.43 ± 3.22 hours), whereas the oral plasma clearance markedly decreased (23.17 ± 6.49 vs. 16.00 ± 5.27 L/h). In the presence of ciprofloxacin, there was a pronounced decrease in the ratio of AUC (metabolite)/AUC (unchanged drug) and highly significant decreases in Cmax and AUC of the metabolite (P < 0.05). Ciprofloxacin may increase the adverse effects of concomitantly administered quinine, which can have serious consequences on the patient. Thus, a downward dosage adjustment of quinine seems to be necessary when concurrently administered with ciprofloxacin.

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Metabolism of quinine

Cited by 4 publications

References 2 publications

Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

Effects of concurrent administration of nevirapine on the disposition of quinine in healthy volunteers

Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration

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