scholarly journals Pharmacokinetics of DA-7867, a New Oxazolidinone, after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

2004 ◽  
Vol 48 (2) ◽  
pp. 659-662 ◽  
Author(s):  
Soo K. Bae ◽  
Won-Suk Chung ◽  
Eun J. Kim ◽  
Jae K. Rhee ◽  
Jong W. Kwon ◽  
...  
Keyword(s):  
Body Weight ◽  
Gastrointestinal Tract ◽  
Oral Dose ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Pharmacokinetic Parameters ◽  
First Pass Effect ◽  
First Pass

ABSTRACT Pharmacokinetic parameters of DA-7867 were dose independent after both intravenous administration and oral administration (at doses of 1 to 20 mg/kg of body weight) to rats. After oral administration of DA-7867 to rats at a dose of 10 mg/kg, approximately 8.27% of oral dose was not absorbed from the gastrointestinal tract, F was 70.8%, and approximately 21.8% of the oral dose was eliminated by the intestine (intestinal first-pass effect).

scholarly journals Dose-Dependent Pharmacokinetics of Tofacitinib in Rats: Influence of Hepatic and Intestinal First-Pass Metabolism

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 318 ◽  
Author(s):  
Ji Sang Lee ◽  
So Hee Kim
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Hepatic Metabolism ◽  
Time Curve ◽  
First Pass Effect ◽  
First Pass Metabolism ◽  
First Pass ◽  
Dose Dependent ◽  
Intraduodenal Administration ◽  
Pass Metabolism

This study investigated the pharmacokinetics of tofacitinib in rats and the effects of first-pass metabolism on tofacitinib pharmacokinetics. Intravenous administration of 5, 10, 20, and 50 mg/kg tofacitinib showed that the dose-normalized area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly higher at 50 mg/kg than at lower doses, a difference possibly due to saturation of the hepatic metabolism of tofacitinib. Oral administration of 10, 20, 50, and 100 mg/kg tofacitinib showed that the dose-normalized AUC was significantly higher at 100 mg/kg than at lower doses, a difference possibly due to saturation of the intestinal metabolism of tofacitinib. Following oral administration of 10 mg/kg tofacitinib, the unabsorbed fraction from the rat intestine was 3.16% and the bioavailability (F) was 29.1%. The AUC was significantly lower (49.3%) after intraduodenal, compared to intraportal, administration, but did not differ between intragastric and intraduodenal administration, suggesting that approximately 46.1% of orally administered tofacitinib was metabolized through an intestinal first-pass effect. The AUC was also significantly lower (42%) after intraportal, compared to intravenous, administration, suggesting that the hepatic first-pass effect on tofacitinib after entering the portal vein was approximately 21.3% of the oral dose. Taken together, these findings suggest that the low F of tofacitinib is due primarily to intestinal first-pass metabolism.

scholarly journals Dose-Dependent Pharmacokinetics of Itraconazole after Intravenous or Oral Administration to Rats: Intestinal First-Pass Effect

2004 ◽  
Vol 48 (5) ◽  
pp. 1756-1762 ◽  
Author(s):  
Jee H. Shin ◽  
Ka Y. Choi ◽  
Yu C. Kim ◽  
Myung G. Lee
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Intragastric Administration ◽  
Time Curve ◽  
First Pass Effect ◽  
First Pass ◽  
Absolute Oral Bioavailability ◽  
Oral Doses ◽  
Dose Dependent ◽  
Intraduodenal Administration

ABSTRACT The dose-dependent pharmacokinetics of itraconazole after intravenous (10, 20, or 30 mg/kg) and oral (10, 30, or 50 mg/kg) administration and the first-pass effects of itraconazole after intravenous, intraportal, intragastric, and intraduodenal administration at a dose of 10 mg/kg were evaluated in rats. After intravenous administration at a dose of 30 mg/kg, the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was significantly greater than those at 10 and 20 mg/kg (1,090, 1,270, and 1,760 μg · min/ml for 10, 20, and 30 mg/kg, dose-normalized at 10 mg/kg). After oral administration, the AUC0-∞ was significantly different for three oral doses (380, 687, and 934 μg · min/ml for 10, 30, and 50 mg/kg, respectively, dose-normalized at 10 mg/kg). The extent of absolute oral bioavailability (F) was 34.9% after an oral dose at 10 mg/kg. The AUC0-∞ (or AUC0-8 h) values were comparable between intravenous and intraportal administration and between intragastric and intraduodenal administration, suggesting that the hepatic and gastric first-pass effects were almost negligible in rats. However, the AUC0-8 h values after intraduodenal and intragastric administration were significantly smaller than that after intraportal administration, approximately 30%, suggesting that the intestinal first-pass effect was approximately 70% of that of an oral dose of 10 mg/kg. The low F after oral administration of itraconazole at a dose of 10 mg/kg could be mainly due to the considerable intestinal first-pass effect.

scholarly journals Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

2008 ◽  
Vol 11 (1) ◽  
pp. 88 ◽  
Author(s):  
Myung G. Lee ◽  
Young H Choi ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Protein Expression ◽  
Intravenous Administration ◽  
Insulin Treatment ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Altered Pharmacokinetic ◽  
Intravenous And Oral Administration ◽  
Control State

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

Influence of First-Pass Effect on Availability of Drugs on Oral Administration

1971 ◽  
Vol 60 (9) ◽  
pp. 1338-1340 ◽  
Author(s):  
M. Gibaldi ◽  
R.N. Boyes ◽  
S. Feldman
Keyword(s):  
Oral Administration ◽  
First Pass Effect ◽  
First Pass

Effect of Oral Ketoconazole on First‐pass Effect of Nifedipine After Oral Administration in Dogs

2002 ◽  
Vol 91 (3) ◽  
pp. 868-873 ◽  
Author(s):  
Masanori Kuroha ◽  
Hideki Kayaba ◽  
Shizuka Kishimoto ◽  
Waleed F. Khalil ◽  
Minoru Shimoda ◽  
...  
Keyword(s):  
Oral Administration ◽  
First Pass Effect ◽  
First Pass

scholarly journals Enhancement of solubility of Metaclopramide using solid dispersion technique with different carriers (HPβCD, PVP K-30)

2019 ◽  
Vol 9 (6) ◽  
pp. 17-22
Author(s):  
Moumita Paul ◽  
Pintu Sarkar ◽  
Riyanka Sengupta ◽  
Saikat Bhunia ◽  
Payal Jana ◽  
...  
Keyword(s):  
Oral Administration ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Water Soluble ◽  
Particle Size Reduction ◽  
First Pass Effect ◽  
Systemic Bioavailability ◽  
First Pass ◽  
Poorly Water Soluble ◽  
Poor Water Solubility

Modern drug discovery has led to the development of drug molecules that exhibit high lipophilicity and poor water solubility, which leads to problematic bioavailability. Approaches have thus been made to enhance dissolution of poorly water soluble drugs through modifications and creation of specific formulations. Metaclopramide is an antiemetic and gastroprokinetic agent, commonly used to treat nausea and vomiting. It is absorbed well after oral administration but a significant first pass effect in some human patients may reduce systemic bioavailability to 30%.The Metaclopramide base is thus modified from Metaclopramide hydrochloride to enhance solubility .This has been achieved by the formulating in solid dispersion since Metaclopramide is poorly water soluble. Though it is absorbed well after oral administration, a significant first pass effect in some patients reduces systemic bioavailability, which can cause adverse side effects. This solid dispersion has then been used through transdermal drug delivery. Enhancement of solubility of poorly water soluble drug by solid dispersion may be attributed to particles modified characters such as particle size reduction, improved wettability, higher porosity, decreased lattice energy, amorphous state. The main objective thus includes modification of drug Metaclopramide  hydrochloride to Metaclopramide base, preparation of solid dispersion of modified Metaclopramide  base drug which has poor water solubility, experimental analysis of Metaclopramide base drug and solid dispersion products with carriers. Keywords: solubility, Metaclopramide, solid dispersion, carriers, HPβCD, PVP K-30

scholarly journals Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

2010 ◽  
Vol 13 (3) ◽  
pp. 443 ◽  
Author(s):  
Tao Guo ◽  
Longshan Zhao ◽  
Dong-Ya Xia
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
High Performance ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Significant Difference ◽  
Total Body

Purpose. The pharmacokinetics of modafinil were investigated in relation to gender and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui ( n = 10/group) following administration of a single 200 mg oral dose. Methods. Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by High performance liquid chromatography with an ultraviolet detector. Pharmacokinetic parameters were evaluated using noncompartmental methods. Results. Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (Cmax) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC0-∞), were higher in women compared to men (p < 0.01). No gender-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and the t1/2 was found to exhibit an ethnicity-based significant difference. Conclusion. The results of the current study suggest that there might be pharmacokinetic differences related to gender and ethnicity in the pharmacokinetics of modafinil.

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