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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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.

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 (AUC T ), maximum plasma concentration (C max ) and terminal elimination half-life (T ½β ) of quinine compared with values with quinine dosing alone (AUC: 53.29 ± 4.01 vs 35.48 ± 2.01 h mg/l; C max : 2.83 ± 0.16 vs 1.81 ± 0.06 mg/l; T ½β : 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 C max 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.

Objectives: Epilepsy is the most common non-infectious neurologic disease in developing African countries following stroke and Alzheimer's disease. Most conventional antiepileptic drugs, due to their centrally acting potentials have been implicated in the deregulation of reproductive hormones. This study assessed the effect of the single and combined administration of vigabatrin (VIG) and carbamazepine (CBZ) on the pituitary-gonadal axis of male Wistar rats.Methods: Fifty male Wistar rats were randomly divided into 5 groups (n=10). The animals were administered with distilled water (0.1 ml/kg/day), VIG (200 mg/kg/day), CBZ (200 mg/kg/day), VIG-CBZ combination (100 mg/kg/day each) and VIG-CBZ combination (200 mg/kg/day each) for 8 weeks. Twenty-four hours after the last dose, 5 rats from each group were sacrificed, while the remaining 5 eventually sacrificed after another 8 week of drug withdrawal. The level of luteinizing hormone, follicle stimulating hormone and testosterone were determined from the serum. The weight of the reproductive organs and sperm indices were assayed, while the testicular tissue were examined for signs of histological alteration. Results:The results showed significant decrease in the levels of luteinizing hormone, follicle stimulating hormone, testosterone and sperm physiological indices. Morphological alteration was noticed in the testes of all the treated rats. However, there was restoration of these parameters sequelae to 8 weeks cessation of treatment. Conclusion:Single and combined administration of VIG and CBZ resulted into pituitary-gonadal axis hormonal deregulation and alterations in the sperm profile which were however reversible upon cessation of treatment.