PHARMACOKINETICS AND PHARMACODYNAMICS EVALUATION OF MATRIX-TYPE PATCHES CONTAINING QUININE IN MALE WISTAR RATS

• Main Author: Fransiska Manurung, Yulia
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45228
• Institution: Institut Teknologi Bandung

Nocturnal leg cramps are painful muscle contractions occured in the leg in the night, that may cause sleep deprivation. Quinine administered orally is an effective pharmacological therapy for the treatment of nocturnal leg cramps, however it has significant side effects. Transdermal matrix patch can reduce dose dumping, thus reduce the side effects. In the previous study, matrix type of quinine patch have been formulated and its in vitro diffusion have been evaluated. The purpose of the present study was to evaluate the pharmacokinetics and pharmacodynamics of matrix-type patch containing quinine in male Wistar rats. Quinine patch was prepared by mixing quinine HCl in HPMC matrix with propylene glycol as plasticizer. Physical and chemical evaluations of patch included uniformity of weight and thickness, moisture content, patch morfology by SEM, tensile strength, % elongation, folding endurance, drug content, and in vitro diffusion test were carried out. The pharmacokinetic evaluation was performed in male wistar rats divided into two groups (n = 5, each), first group was administered with quinine orally (27 mg/kg BW) and second group was applied quinine transdermally (54 mg/kg BW). The pharmacodynamic evaluation was carried out with triction and rotarod methods in male wistar rats which divided into 5 groups (n = 8 for triction and n = 5 for rotatod). The first group was normal group; the second group was administered with quinine orally (27 mg/kg BW); the 3 rd , 4 th , and 5 th group was applied quinine transdermally with high dose (54 mg/kg BW), moderate dose (18 mg/kg BW), and low dose (3.6 mg/kg BW) respectively. Hematology profiles were analyzed to the groups of normal, oral (27 mg/kg BW), and transdermal (moderate dose 18 mg/kg BW) in the third week following repeated daily dose. Tmax and Cmax were significantly diferrent (p < 0.05) between oral group and transdermal group, tmax and Cmax of quinine oral were 2 h dan 559.950 ± 192.926 ng/mL, while tmax and C max of quinine transdermal were 8 hours 208.744 ± 40.159 ng/mL. There was no significant differences in AUC0-24 between oral (27 mg/kg BW) and transdermal (54 mg/kg BW) group (p > 0.05). The effect of quinine given orally and transdermal high and moderate doses were comparable in both methods, whereas low dose of quinine transdermal was not significantly difference with the normal group (p > 0.05). Platelet counts for all groups were within normal range, platelet counts between normal group and transdermal moderate dose were comparable (p > 0.05), but significantly different with oral group (p < 0.05).