A comparative bioavailability study of two ibuprofen formulations after single-dose administration in healthy volunteers.

This study was aimed to investigate the bioequivalence of ibuprofen 125 mg suppository formulation (Ibukal®, test formulation from PT. Kalbe Farma, Tbk., Jakarta) and the ibuprofen suppository comparative formulation (Proris®, from PT. Pharos Indonesia, Jakarta) in 12 healthy volunteers. The pharmacokinetic parameters used in this study were the area under the concentration-time curve from time zero to hour 10 (AUC0-t), the area under the concentration-time curve from time zero to infinite (AUC0-inf), the maximum concentration (Cmax), and the time needed to reach the maximum concentration (tmax). The study was designed as a random cross-over fashion, single-blinded which included 12 healthy adult volunteers. The volunteers were fasted overnight and in the morning they received a suppository of the test drug (Ibukal®) or a suppository of the comparative drug (Proris®). Blood samples were withdrawn on hour 0 (control), 20 min; 40 min; 1; 1.5; 2; 2.5; 3; 4; 6; 8; and 10 time points after the administration of the drug. Following a wash-out period of 1 week, this procedure was repeated using the other drug. The serum concentration of the drug was determined by means of high-performance liquid chromatography with ultraviolet detection. The results of the study showed that, the mean (SD) of AUC0-t, AUC0-inf, Cmax and tmax of the test drug were, respectively, 28.59(3.37) μg.h.mL-1, 30.47(3.56) μg.h.mL-1, 8.24(1.44) μg/mL, and 1.33(0.44) h. The mean (SD) of AUC0-t, AUC0-inf, Cmax and tmax of the comparative drug were, respectively, 28.13(8.14) μg.h.mL-1, 30.56(8.05) μg.h.mL-1, 8.27(2.88) μg/mL, and 1.79(0.33) h. The geometric means ratio of the test to the comparative drug were 104.38% (CI 90%: 90.38-120.54%) for AUC0-t, 101.97% (CI 90%: 89.51-116.16%) for AUC0-inf, and 104.02% (CI 90%: 85.73-126.16%) for Cmax. There was no side effect of the drug detected in this study. From the results we can conclude that the 125 mg of ibuprofen suppository of PT Kalbe Farma, Tbk. (Ibukal®) is bioequivalent to that of the comparative drug (Proris®).

Interaction of erythromycin and clarithromycin with orange juice.

Concomitant administration of orange juice with fexofenadine has been found to decrease the bioavailability of fenofenadine to less than 30% via inhibition of organic-anion transporting polypeptide (OATP), a drug uptake transporter expressed in organs such as liver, kidney and intestine. Erythromycin and clarithromycin are substrates and inhibitors of CYP3A4, a drug metabolizing enzyme in the liver and enterocytes, and P-glycoprotein (P-gp), a drug efflux transporter expressed in the same organs as OATP. Since an extensive overlap exists between substrates and inhibitors of CYP3A4, P-gp and OATP transporters, we want to study the effect of coadministration of our local orange (Siam orange) juice on the bioavailability of the above antibacterials. We conducted two 2-way cross-over randomized studies, one study for each antibacterial (500 mg), crossed between administration with orange juice (200 ml) and with water, in 12-13 healthy subjects per study. The serum concentrations of the antibacterials were assayed by microbiological method. The mean (range) ratio of AUC0-t with orange juice/with water were as follows : erythromycin : total (n=13) 81.7 (9.7-193.8)%, unchanged (n=4) 96.4 (80.5-107.9)%, decreased (n=6) 31.9 (9.7-49.0)%, increased (n=3) 161.8 (134.6-193.8)%; clarithromycin : total (n=12) 91.4 (20.6-158.3)%, unchanged (n=5) 103.1 (80.9-123.0)%, decreased (n=4) 34.8 (20.6-64.3)%, increased (n=3) 147.2 (132.9-158.3)%. It was concluded that coadministration of Siam orange juice with erythromycin or clarithromycin produced unpredictable effects on the bioavailability of these antibacterials in individual subjects, with marked decreases in almost half of the subjects, although in totals the effects were not statistically significant.