• 한국임상약학회지
• /
• 제7권2호
• /
• pp.51-63
• /
• 1997

The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

• Biomolecules & Therapeutics
• /
• 제16권3호
• /
• pp.215-218
• /
• 2008

To investigate the possible interaction between rutaecarpine and phenobarbital in rats, phenobarbital in saline at 80 mg/kg was given ip to male SD rats for 3 consecutive days. Saline was given to control animals. One day after phenobarbital pre-treatment, rutaecarpine at 16 mg/kg was administered through penile vein. Blood was collected and analyzed by using HPLC. The pharmacokinetic parameters were determined with the non-compartmental model. Pre-treatment with phenobarbital significantly altered the pharmacokinetic profiles of rutaecarpine and its metabolite, 10-hydroxyrutaecarpine. The AUC of rutaecarpine was reduced to approximately 50% of control and the plasma half-life of rutaecarpine was significantly shortened when compared with control. In addition, the Cmax of 10-hydroxyrutaecarpine was increased approximately 160% of control. The AUC and the plasma half-life of 10-hydroxyrutaecarpine were decreased to 76.9% of control and to 82.7 min from 175.9 min, respectively. The results suggested that phenobarbital might accelerate the metabolism of rutaecarpine, thereby changing the pharmacokinetic parameters of rutaecarpine in male SD rats.

• 생물정신의학
• /
• 제6권1호
• /
• pp.49-66
• /
• 1999

Polypharmacotherapy, both psychotropic and nonpsychotropic, is widespread in various situations including psychiatric hospitals and general hospitals. As the clinical practice of using more than one drug at a time increase, the clinician is faced with ever-increasing number of potential drug interactions. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. The objective of this review is evaluation for drug-drug interactions often encountered in psychiatric consultation. Drug interactions can be grouped into two principal subdivisions : pharmacokinetic and pharmacodynamic. These subgroups serve to focus attention on possible sites of interaction as a drug moves from the site of administration and absorption to its site of action. Pharmacokinetic processes are those that include transport to and from the receptor site and consist of absorption, distribution on body tissue, plasma protein binding, metabolism, and excretion. Pharmacodynamic interactions occur at biologically active sites. In psychiatric consultation, these two subdivisions of drug interactions between psychotropic drugs and other drugs are likely to happen. We gathered informations of the drugs used in physically ill patients who are consulted to psychiatric department in Korea University Hospital. And we reviewed the related literatures about the drug-drug interactions between psychotropic drugs and other drugs.

• 한국임상약학회지
• /
• 제19권1호
• /
• pp.32-36
• /
• 2009

The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with simvastatin (0.3 and 1.0 mg/kg). Compared with the control (given nicardipine alone), coadministration of simvastatin (1.0 mg/kg) significantly (p<0.05) increased the area under the plasma concentration (AUC) and peak plasma concentration ($C_{max}$) of nicardipine. The relative bioavailability (RB%) of nicardipine increased from 1.19- to 1.48-fold. However there were no significant changes in $t_{max}$, and $t_{1/2}$ of nicardipine. The enhanced oral bioavailability of nicardipine might be due to an inbition of cytochrom P450 3A mediated-metabolism of nicardipine in the intestine and in the liver by simvastatin. Based on these results, the concurrent use of simvastatin significantly enhanced the oral exposure of nicardipine in rats. The dosage regimen of nicardipine should be taken into consideration for potential drug interaction when combined with simvastatin in clinics.

• 분석과학
• /
• 제35권2호
• /
• pp.60-68
• /
• 2022

In this study, we developed and validated a sensitive analytical method to quantify baphicacanthin A in mouse plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for baphicacanthin A ranged from 0.5 to 200 ng/mL and were linear, with an r² of 0.985. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. Besides, we investigated the pharmacokinetics of baphicacanthin A following its intravenous (5 mg/kg) and oral administration (30 mg/kg). Intravenously injected baphicacanthin A showed biphasic elimination kinetics with high clearance and volume of distribution values. Furthermore, baphicacanthin A showed a rapid absorption but low aqueous solubility (182.51±0.20 mg/mL), resulting in low plasma concentrations and low oral bioavailability (2.49 %). Thus, we successfully documented the pharmacokinetic properties of baphicacanthin A using this newly developed sensitive LC-MS/MS quantification method, which could be used in future lead optimization and biopharmaceutic studies.

• 셀메드
• /
• 제4권3호
• /
• pp.17.1-17.8
• /
• 2014

Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John's wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.

• 대한임상독성학회지
• /
• 제3권1호
• /
• pp.11-16
• /
• 2005

Chemical mixtures of components, each of which are present at less than guidance concentrations, may be hazardous due to additivity, interactions, or both. Toxicological interactions may increase the health hazard above what would be expected from an assessment of each component singly, or all components additively. So chemical mixture are a particular issue in public health. There are several approach to assess whether there are additivity or interaction in assessing toxicological effects, such as, components-based approach, physiologically-based pharmacokinetic /pharmacodynamic(PBPK/PD) models, hazard index method, and weight-of evidence method. If we consider interaction or additivity effects in assessing the health effects of chemcial mixtures, we can get more accurate information about toxicological effects and dose-response relationship in chemical mixtures.

• Journal of Pharmaceutical Investigation
• /
• 제26권2호
• /
• pp.113-117
• /
• 1996

This study was attempted to investigate the pharmacokinetic interaction between sodium valproate (4, 8, 16 mg/kg, i.v.) and phenytoin (4 mg/kg, i.v.) in rabbits. The plasma concentration and area under the curve (AUC) of phenytoin were increased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (4, 8, 16 mg/kg) in rabbits. The volume or distribution and total body clearance of phenytoin were decreased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (8, 16 mg/kg) in rabbit. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin will be coadministered with sodium valproate in clinical use.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.306.2-307
• /
• 2003

The purpose of this study was to investigate the effect of verapamil (5, 10, 20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (50 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel with verapamil increased dose-dependently, and increased significantly in both coadministration (p<0.05) and pretreatment group (p<0.01) compared to that of control. (omitted)

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.240.1-240.1
• /
• 2003

The purpose of this study was to investigate the effect of nifedipine (10 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (50 mg/kg) orally coadministered and pretreated in rats. The plasma concentration of paclitaxel in combination with nifedipine was significantly (p<0.05 at 10 mg/kg coadmin., p<0.01 at pretreat.) increased compared to that of control, from 2 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel with nifedipine was significantly (p＜0.05 at 10 mg/kg coadmin., p＜0.01 at pretreat.) higher than that of control (omitted)