pharmacokinetics
A Repeated-Dose Model of Percutaneous Drug Absorption
Wed, 2014-08-06 12:45 — Dr Samir A Matar
Journal Title, Volume, Page:
Applied Mathematical Modelling Volume 26, Issue 4, Pages 529–544
Year of Publication:
2002
Preferred Abstract (Original):
A mathematical model is developed for percutaneous absorption with regular applications of the drug. The linear partial differential equations (PDEs) of the model are solved using a finite-difference method which is second-order accurate in space and time. The solutions of these PDEs give the concentrations of the drug in the vehicle and the skin at a given time. The numerical results obtained are adapted to monitor the amount of drug released from the vehicle, the bio-availability for each application, the amount of drug in the skin at a given time, and the flux from the skin to the capillary at a given time.
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Pharmacokinetics of the Citrus Flavanone Aglycones Hesperetin and Naringenin After Single Oral Administration in Human Subjects
Mon, 2013-12-30 14:34 — Feras I. Qanaze
Journal Title, Volume, Page:
European Journal of Clinical Nutrition, 61, 472–477
Year of Publication:
2007
Preferred Abstract (Original):
Background and Objective
Hesperetin and naringenin, the aglycones of the flavanone glycosides hesperidin and naringin, occur naturally in citrus fruits. They exert interesting pharmacological properties such as antioxidant, anti-inflammatory, blood lipid and cholesterol lowering and are considered to contribute to health benefits in humans. However, no information is available on the pharmacokinetics of the citrus flavanones hesperetin and naringenin after their oral administration to humans as pure aglycones. Therefore, the objective of the present investigation was the evaluation of the pharmacokinetic parameters of hesperetin and naringenin in plasma and urine, after their single oral administration in humans in the form of solid dispersion capsules, and also to improve the absorption rate of flavanones by using aglycones rather than the naturally occurring glycosides.
Design
Six healthy volunteers received orally 135 mg of each compound, hesperetin and naringenin, under fasting conditions. Blood samples were collected at 14 different time points over a 12 h period. Urine was collected over 24 h, in five sequential timed intervals. Plasma and urine hesperetin and naringenin concentrations, after enzymatic hydrolysis of their conjugated forms, were measured using validated high-pressure liquid chromatography methods. Pharmacokinetic parameters for hesperetin and naringenin, such as C(max), T(max), AUC(0-t), AUC(0-infinity), CL/F, V/F, t(1/2), MRT, A(e), A(e)((0-24)), and R(max) were calculated from their plasma or urine concentrations.
Results
Pharmacokinetic analysis showed that both hesperetin and naringenin were rapidly absorbed and their concentrations in plasma observed 20 min after dosing and reached a peak in 4.0 and 3.5 h, respectively. The mean peak plasma concentration (C(max)) for hesperetin and naringenin were 825.78+/-410.63 ng/ml (2731.8+/-1358.4 nmol/l) and 2009.51+/-770.82 ng/ml (7386.6+/-2833.4 nmol/l), respectively and the mean AUC(0-infinity) values were 4846.20+/-1675.99 ng h/ml and 9424.52+/-2960.52 ng h/ml for hesperetin and naringenin, respectively. The elimination half-life for hesperetin was found to be 3.05+/-0.91 h and for naringenin 2.31+/-0.40 h, respectively. The mean values of the relative cumulative urinary excretion, as percentage of the administered dose, for hesperetin and naringenin, were found to be 3.26+/-0.44 and 5.81+/-0.81%, respectively.
Conclusions
Oral administration of the flavanone aglycones, hesperetin and naringenin, lead to their rapid absorption as their conjugated forms. The cumulative urinary recovery data indicated low bioavailability for both flavanone aglycones, owing to extensive first-pass metabolism partly by cleavage of the C-ring by the enzymes of intestinal bacteria leading to degradation products such as phenolic acids.
Effect of Licorice Extract on the Pharmacokinetics of Ciprofloxacin in Rabbits after Oral Administration Using an Improved High-Performance Liquid Chromatography Assay
Mon, 2013-02-11 13:29 — Nasr SHRAIM
Journal Title, Volume, Page:
Jordan Journal of Pharmaceutical Sciences 5 (2): 120-130.
Year of Publication:
2012
Preferred Abstract (Original):
This study was undertaken to evaluate the significance of pharmacokinetic interaction between ciprofloxacin and licorice (Glycerhyza glabra). The study was designed as a comparative, randomized, two-period, two-treatment, two-sequence, single dose, crossover study in order to investigate the effect of licorice extract on ciprofloxacin in 12 rabbits (1.8-3.2kg). Rabbits were administered single oral doses of 40 mg/kg ciprofloxacin either with licorice extract or water. A simple and sensitive high performance liquid chromatography method for the detection and quantification of ciprofloxacin in rabbit plasma was developed specifically for this study. The resulting concentrations versus time curves were analyzed using non–compartmental pharmacokinetic analysis. Study results showed that licorice extract slightly reduced the rate and extent of ciprofloxacin absorption to around 80% [maximum plasma concentration (Cmax); from 1714 ng/ml to 1241 ng/ml, with a p-value of 0.25 and a 90% confidence interval (90% CI) 43.930–119.3 and the area under the plasma concentration time curve from zero to infinity (AUC∞); from 6964 ng.hr/ml to 5777 ng.hr/ml, with a p-value of 0.33 and a 90% CI 58.8–117.4 ng.hr/ml]. This interaction is speculated to be due to the interaction between the metals in the licorice extract and ciprofloxacin.
In conclusion, the non-statistically significant pharmacokinetic interaction between ciprofloxacin and licorice that was observed in this study is not expected to have significant clinical consequences. 
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