Pharmacokinetic interactions involving selected antimalarial and antimicrobial agents during co-administration in healthy volunteers.
| dc.contributor.author | ADEMISOYE Adebusyi Akande | |
| dc.date.accessioned | 2025-09-09T10:55:36Z | |
| dc.date.available | 2025-09-09T10:55:36Z | |
| dc.date.issued | 2022 | |
| dc.description | i-xxii, i- | |
| dc.description.abstract | This study determined the baseline pharmacokinetics of amodiaquine, quinine, itraconazole, piperaquine, their metabolites and evaluated the effect co-administration of rifampicin on the pharmacokinetics of amodiaquine. It also evaluated the bi-directional drug interactions between itraconazole and quinine as well as the effect of clarithromycin on the pharmacokinetics of piperaquine in healthy volunteers. These were with the view to providing information on the magnitude of interactions during co-administration of antimalarials and selected antimicrobial agents. Volunteers were randomly selected and administered single oral dose of amodiaquine (600 mg) and rifampicin (150 mg) daily for five days with concurrent oral single dose amodiaquine (600 mg) after six week wash out period on the 5th day. Another set of volunteers were administered oral single dose quinine (600 mg). Following a three-week wash out period, itraconzole (100 mg) was administered daily for ten days. Blood samples were collected following the 5th dose of itraconazole over a period of 24 hours and during the co-administration of a single oral dose of quinine on the 8th day, while continuing itraconazole drug administration. Another set of volunteers were adminsitered single oral dose of P-Alaxin© consisting piperaquine (320 mg) and dihydroartemisinin (80 mg). Following a five-month wash out period, clarithromycin (500 mg) was given twice daily for five days. A single dose of P-Alaxin© was administered on the 3rd day. In all the cases, blood samples were collected at 0, 1, 2, 4 8, 12, 24, 48 h and analyzed for plasma levels of the administered drugs and their metabolites; 3-hydroxyquinine and hydroxyitraconzole using validated RP-HPLC methods. The difference between pairs were evaluated by student‘s t-test and Wilcoxon matched pair signed rank test. A p-value of <0.05 was considered significant. The values within 80%-125% range of test/reference ratio of the geometric means at 90% confidence intervals were considered bioequivalent. The elimination half-life of amodiaquine declined significantly following concurrent administration with rifampicin (p<0.05), the Cmax and AUC0-48 decreased 2 and 3 folds respectively. The AUC0-48 of desethylamodiaquine increased two folds while the metabolic ratio increased from 1.55 to 2.68. Following concurrent administration of quinine with itraconazole, AUC0-48 and Cmax of quinine increased 3 folds and about 30% percent increase for both Cmax and AUC0-48 of itraconazole. The Cmax, AUC0-48, and T1/2 of piperaquine when concurrently administered with clarithromycin increased significantly (179.41±56.35 ng/ml vs 478.99 ± 148.86 ng/ml; 37,644.56 ± 16.716.95 ng/ml*h vs 104,098.47 ± 53.311.57 ng/ml*h; 247.96 ± 64.98 h vs 468.59±164.94 h) respectively (p<0.05). The Cmax obtained for amodiaquine, quinine and piperaquine fell within 80% 125% bioequivalence range. The study concluded that interactions occurred between amodiaquine and rifampicin; quinine and itraconazole; and piperaquine and clarithromycin which could lead to treatment failure or adverse effects in humans | |
| dc.identifier.citation | Ademisoye, A.A. (2022). Pharmacokinetic interactions involving selected antimalarial and antimicrobial agents during co-administration in healthy volunteers. Department of pharmaceutical chemistry, Faculty of pharmacy, Obafemi Awolowo University. | |
| dc.identifier.uri | https://ir.oauife.edu.ng/handle/123456789/6818 | |
| dc.language.iso | en | |
| dc.publisher | Department of pharmaceutical chemistry, Faculty of pharmacy, Obafemi Awolowo University. | |
| dc.title | Pharmacokinetic interactions involving selected antimalarial and antimicrobial agents during co-administration in healthy volunteers. | |
| dc.type | Thesis |