• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.102-107
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• 2007

Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.

• YAKHAK HOEJI
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• v.14 no.1_2
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• pp.28-35
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• 1970

The absorption of Aminopyrine from the small intestine of a rat in combination with antihistamic agent, Diphenhydramine, Pheniramine, Tripelennamine and Diphenhydramine respectively, was examined. Through the rat small intestine canal, a definite quantity of a sample solution comprising 0.5 mM of Aminopyrine and 0.1 mM of each antihistamic agent in phosphate buffer solution (pH=7.4) was perfused through the rat small intestine at rate 5 ml per minute. The samples of the circulating solution were taken out after 5 minutes of the perfusion to give initial concentration and every 30 minutes for 3 hours. The amount of residual Aminopyrine in the solution was determined photometrically at 720 m.mu. by using 0.4% potassium ferricyanate solution and 1% ferric nitrate in 0.1N nitric solution. The mixed compounds of Aminopyrine with antihistamic agent, such as Aminopyrine with Diphehydramine, Aminopyrine with Pheniramine, Aminopyrine with Tripelennamine and Aminopyrine with Chloropheniramine showed more increased absorption than Aminopyrine alone. the absorption rate constants and apparent permeability coefficients of the mixed compounds were shown in detail.

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.421-425
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• 2003

The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using an ex vivo buccal diffusion model. The permeation rate of [$^3 H$]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P＜0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [$^3 H$]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [$^3$H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.