EFFECT OF HIBISCUS SABDARIFFA (LINN) WATER EXTRACT ON THE PHARMACOKINETICS OF METFORMIN AND LISINOPRIL IN HEALTHY HUMAN VOLUNTEERS
EFFECT OF HIBISCUS SABDARIFFA (LINN) WATER EXTRACT ON THE PHARMACOKINETICS OF METFORMIN AND LISINOPRIL IN HEALTHY HUMAN VOLUNTEERS
No Thumbnail Available
Date
2018-05
Authors
NASIR, Ibrahim
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Abstract
The concurrent use of herbal drugs and orthodox medicines for the treatment of various health conditions is a common practice amongst patients; a practice that could result in drug-herb interaction. This study evaluates the effects of Hibiscus sabdariffawater extract on thein vitro and in vivo availability, as well as pharmacokinetics of metforminand lisinopril in healthy human volunteers.For the determination of metformin and lisinopril in vitroin simulated physiological pHs(0.1 M HCl, phosphate buffers pH of 6.8 and 7.4), three simples UV spectrophotometric methodswere developed and validated according to ICH guidelines. The in vitroavailability of metformin and lisinopril alone and in presence of Hibiscus sabdariffa calyxes water extracts (1 g/L) in each of the three media(1 L and 900 mL) were determinedusing dissolution apparatus (BP, 2013) set at 100and 50 rpm at 37 °C. Samples (5 mL) withdrawn from the media at 5, 10, 15, 30, 45, and 60 min were analysed for the metformin and lisinopril content released using the appropriate developed method. For the quantification of metformin and lisinopril in the in vivostudy, a RP-HPLC method was developed and validated for each drug using caffeine as internal standard IS.The optimized conditions comprise of a Chemsl ODS®C18 column (200 x 4.6 mm), binary mobile phase (Methanol: Water 80:20)containing 0.1 % orthophosphoric acid as additive, isocratic elution mode, 232 and 218 nm detection wavelengths flow rate of 1.0 mL/min and 10 μL injection volume. Thein vivo study involved 48 apparently healthy human volunteers randomly selected and divided into four groups of 12 subjects each. The study was carried out in four phases; phase 1 (administration of the drugs alone), phase 2 (concurrent administration of drugs with Hibiscus sabdariffa calyxes water extracts), phase 3 (administration of drugs30 min after administration of Hibiscus sabdariffa water extracts) and phase 4 (administration of Hibiscus sabdariffawater extracts 30 minutes after administration of drugs). Saliva samples collected at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 12.0, 24.0 and 36.0 hrin each phase were analysed
vii
for metformin and lisinopril content using the appropriate developed RP-HPLC method.The results indicated that the UV spectrophotometric methods obeyed Beer‟s law within the calibration range (2.5 to 15 μg/mL) with correlation coefficients of 0.999. The λmaxfor metformin/lisinopril observed in 0.1 M HCl, phosphate buffer pH of 6.8 and 7.4 were 205/215, 235/210 and 232/210 nm respectively.The presence of Hibiscus sabdariffa significantly (p < 0.05) increased the in vitro availability of metformin and lisinopril in simulated gastric and intestinal pHs. In simulated blood pH however, the availability of metformin was significantlydecreased(p < 0.05) by the presence of Hibiscus sabdariffawhile that of lisinopril was significantly increased. In vivo availability of metformin and lisinopril were significantly (p < 0.05) increased by the presence of Hibiscus sabdariffain all phases.For the RP-HPLC methods, retention times of 1.6 and 1.7 min were observed for metformin and lisinopril respectively. Pharmacokinetic parameters of the drugs administered alone and when interacted with Hibiscus sabdariffa calyxes water extracts showed that metformin administered alone achieved Cmax of 892.320ng/mL at 5 hr (Tmax), while lisinopril attained Cmax of 95.360ng/mL at 7 hr (Tmax). Furthermore,𝐴𝑈𝐶0∞of5460216.284ng.hr/mLand736805.828ng.hr/mLwere recorded for metformin and lisinopril respectively.Small increases in Cmaxand 𝐴𝑈𝐶0∞were observed when both metformin and lisinopril were interacted with Hibiscus sabdariffain all the phases.However, the increases observed in all the pharmacokinetic parameters for all phases were not statistically significant (p < 0.05). It can therefore be concluded that Hibiscus sabdariffa calyxes water extract does not significantly affect the pharmacokinetics of metformin and lisinopril in healthy humans.
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DOCTOR OF PHYLOSOPHY (Ph.D) DEGREE IN PHARMACEUTICAL CHEMISTRY
Keywords
EFFECT,, HIBISCUS SABDARIFFA (LINN),, WATER EXTRACT,, HARMACOKINETICS,, METFORMIN,, LISINOPRIL,, HEALTHY HUMAN VOLUNTEERS