title: Significant Pharmacokinetic Interactions Between Quinine and Ampicillin-Cloxacillin Combination.
abstract: BACKGROUND
  The co-existence of malaria with bacterial infections is common in the tropics, hence the concurrent use of antimalarials and antibiotics.
  
  
  OBJECTIVE
  This study aimed to investigate the effect on pharmacokinetics and antimicrobial activity of co-administration of quinine and combined ampicillin-cloxacillin.
  
  
  METHODS
  In total, 14 healthy adults received single oral doses of ampicillin-cloxacillin combination alone and with quinine in a randomized crossover manner. Urine samples collected at predetermined intervals over 48 h were analysed. The effect of quinine on minimum inhibitory concentrations (MICs) of ampicillin and cloxacillin were determined against Staphylococcus aureus by agar diffusion, agar dilution, and broth dilution.
  
  
  RESULTS
  Quinine significantly reduced the rate and extent of excretion of ampicillin and cloxacillin (p < 0.0002). The total amounts of ampicillin and cloxacillin excreted unchanged (Du(∞)) alone were 217.10 ± 53.82 and 199.0 ± 64.29 mg versus 126.40 ± 50.63 and 135.20 ± 52.24 mg, respectively, with quinine. Respective maximum excretion rates (dDu/dt max) for ampicillin and cloxacillin were 43.55 ± 19.41 and 77.64 ± 29.65 mg/h alone versus 18.01 ± 8.52 and 53.16 ± 20.72 mg/h with quinine. This indicates a significant reduction in Du(∞)and dDu/dt max by 41.78 and 58.65 % for ampicillin and 32.06 and 31.53 % for cloxacillin. Conversely, the disposition of quinine was unaffected by ampicillin-cloxacillin (p > 0.1). The MIC of antibiotics alone versus with quinine, respectively, were 0.11 ± 0.04 and 0.78 ± 0.1 µg/ml for ampicillin, and 0.18 ± 0.1 and 0.92 ± 0.4 µg/ml for cloxacillin, with a five- to sevenfold increase (p > 0.01); indicating a decrease in antimicrobial activity by quinine.
  
  
  CONCLUSIONS
  Quinine therefore, reduced the bioavailability and the antimicrobial activity of ampicillin-cloxacillin upon co-administration, which may have therapeutic implications. Caution is required with the co-administration of these medicines.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria.
authors.forename: Olubunmi B
authors.initials: OB
authors.lastname: Falade
authors.affiliation: Genetic and Bioethics Unit, Institute of Advanced Medical Research and Training (IAMRAT), College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Adeyinka G
authors.initials: AG
authors.lastname: Falusi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria.
authors.forename: Ajibola A
authors.initials: AA
authors.lastname: Olaniyi
authors.affiliation: Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.
authors.forename: Chizoba
authors.initials: C
authors.lastname: Ezeasor
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria.
authors.forename: David A
authors.initials: DA
authors.lastname: Kwasi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria. peacebab2001@yahoo.com.|Genetic and Bioethics Unit, Institute of Advanced Medical Research and Training (IAMRAT), College of Medicine, University of Ibadan, Ibadan, Nigeria. peacebab2001@yahoo.com.
authors.forename: Chinedum P
authors.identifier: http://orcid.org/0000-0001-9173-8032
authors.initials: CP
authors.lastname: Babalola
mesh_terms: D000293:Adolescent; D000328:Adult; D000667:Ampicillin / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D000962:Antimalarials / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003023:Cloxacillin / Q000032:analysis / Q000494:pharmacology* / Q000652:urine; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009549:Nigeria; D011803:Quinine / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D013211:Staphylococcus aureus / Q000187:drug effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D000667:Ampicillin; D011803:Quinine; D003023:Cloxacillin