EFFECTS OF AMOXICILLIN AND CLOXACILLIN ON THE PHARMACOKINETIC PROFILE OF METFORMIN
GARBA MUSA ABDULLAHI1 *, BELLO SANI SAIDU2 , DANBABA ABDULJALAL1 , BAKARE– ODUNOLA MOJITAIBAT3 , GARBA MAGAJI4 , ANAS HARUNA1
1. Department of Pharmaceutical and Medicinal Chemistry, Kaduna State University, Kaduna, Nigeria.
2. Department of Pharmaceutical and Medicinal Chemistry, Bayero University, Kano, Nigeria.
3. Department of Pharmaceutical and Medicinal Chemistry, University of Ilorin, Kwara State, Nigeria.
4. Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria, Nigeria.
Afr. J Pharm Res Dev; Volume 11(2): 137-144 ; 2019
Metformin is prescribed with amoxicillin /cloxacillin in the treatment of diabetic disease with infections. However, the effects of these drugs on the pharmacokinetic profile of metformin are still unknown. The study aimed at investigating the pharmacokinetic interactions of amoxicillin and cloxacillin when co-administered with metformin. It is a one-way single dose cross-over study in two phases. The subjects acted as their own control, and each phase was preceded by an overnight fast. In phase one, metformin was administered to all the diabetic patients, while phase two was divided into two groups. The first group received a single dose of metformin with amoxicillin while the second group received metformin with cloxacillin. Serial blood samples were collected over a period of 24 h during each phase into an ethylene diaminetetra acetic acid (EDTA) vacutainer and stored at -4 ˚C before analysis. After collection, blood samples were processed. A validated high-performance liquid chromatography (HPLC) method was used in the estimation of serum concentration of metformin. The pharmacokinetic of metformin when co- administered with amoxicillin Cmax (µg/ml) and AUC0-8 (h µgml/h) decreased to 1.104.40 ± 0.04 and 4.25 ± 0.45 respectively. On the other hand, with cloxacillin Ka 0.58 ± 0.04 h-1 , Cmax to 1.28 ±0.35 µg/ml, AUC and t1/2β increased to 5.18 ± 0.02 µg.h/m.h, and 6.2 ± 0.02 h respectively. Our findings showed that metformin may be coadministered with amoxicillin to Type 2 diabetic patients without risk of side effects, while co-administration of cloxacillin with metformin need adjustment of the dose to avoid the possible risk of toxicity.
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KEYWORDS: Bioavailability; Drug-drug interactions; HPLC; Toxicity; Therapeutic failure.