			Home About us Contact

Mean AUC0 (mean + auc0)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Formulations in De Novo Kidney Transplantation: A Randomized, Open-Label Trial

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
Z. Wlodarczyk
Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC0,24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC0,24 and Cmin for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID. [source]

Effect of lansoprazole and rabeprazole on tacrolimus pharmacokinetics in healthy volunteers with CYP2C19 mutations

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2004
Fumio Itagaki
The aim of this study was to investigate the effects of the proton pump inhibitors (PPIs), lansoprazole and rabeprazole, on tacrolimus pharmacokinetics in healthy volunteers with mutations in the cytochrome P450 (CYP) 2C19 gene (CYP2C19). An open-label crossover study was performed with 19 healthy subjects. Tacrolimus (2 mg) was administered orally with and without lansoprazole (30 mg per day for 4 days) or rabeprazole (10 mg per day for 4 days). Blood concentrations of tacrolimus were determined before and 1, 2, 4 and 8 h after dosing. Genotyping for CYP2C19 was conducted by a polymerase chain reaction-restriction fragment length polymorphism method. Coadministration of lansoprazole significantly decreased the oral tacrolimus clearance, resulting in an increase in the area under the blood concentration-time curve (AUC0,8) (control vs with lansoprazole: 29.7 ± 3.5 vs 44.1 ± 5.0 ng h mL,1, P<0.05). Large individual variation was observed in the effects of lansorazole on tacrolimus AUC0,8 owing to CYP2C19 genotype status. The percent change for tacrolimus AUC0,8 in subjects with and without CYP2C19 mutant alleles was 81% and 29%, respectively. Coadministration of rabeprazole also increased the mean AUC0,8 of tacrolimus, but the difference was not statistically significant. These observations suggest that drug interaction between tacrolimus and lansoprazole occurs in subjects with higher lansoprazole blood concentrations corresponding to CYP2C19 genetic status. In contrast, rabeprazole has minimal effect on tacrolimus pharmacokinetics regardless of CYP2C19 genotype status. [source]

Evaluation of the safety, pharmacokinetics and treatment effects of an ,,,3 integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010
Mark A ROSENTHAL
Abstract Aim: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an ,,,3 integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer (HRPC) and bone metastases. Methods: A total of 21 patients with bone metastases and HRPC were randomized to receive MK-0429 200 mg b.i.d. or 1600 mg b.i.d. for 4 weeks. Toxicity, pharmacokinetics and markers of bone turnover and tumor activity were examined. Results: Nausea was the most common adverse event: one (200-mg group) and 11 (1600-mg group) patients. At 4 weeks, mean AUC0,12 h was 210 mmol*h (200-mg group) and 673 mmol*h (1600-mg group); mean Cmax values were 42 mmol/L (200-mg group) and 154 mmol/L (1600-mg group). Urinary cross-linked N-telopeptides of type I collagen to creatinine ratio (uNTx), a bone turnover biomarker, showed a change from baseline of ,43.4 percent (200-mg group) and ,34.1 percent (1600-mg group). There was an increase in serum prostate specific antigen (PSA), a marker for disease activity, of 54.1 percent (200-mg group) and 44.5 percent (1600-mg group). Conclusion: MK-0429 was generally well tolerated, with the most common side-effect being nausea. There was some evidence of an early reduction of bone turnover, indicating a potential for clinical use in the treatment of MBD although serum PSA was unexpectedly increased during the study. [source]

Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2008
N. Ceren Alemdaroglu
Abstract Previous in vitro studies using Caco-2 cell monolayers suggested a possible interaction between green and black tea and folic acid at the level of intestinal absorption. The main purpose of the present study was to investigate a possible pharmacokinetic interaction between tea and folic acid in healthy volunteers. In an open-labeled randomized cross-over study, the pharmacokinetic interaction between tea and folic acid (0.4,mg and 5,mg) was investigated in healthy volunteers. Water was used as the reference drink. Subjects ingested 0.4,mg folic acid tablets with water, green or black tea (0.3,g extract/250,ml) or 5,mg folic acid tablets with water or green tea (0.3,g extract/250,ml). Blood samples were collected over a period of 8,h. Serum folate analysis was carried out by a competitive immunoassay which uses direct chemiluminescent technology. At the 0.4,mg folic acid dose, green and black tea reduced the mean Cmax of serum folate by 39.2% and 38.6%, and the mean AUC0 , , by 26.6% and 17.9%, respectively. At the 5,mg folic acid dose, the mean Cmax of serum folate was reduced by 27.4% and the mean AUC0 , , was decreased significantly by 39.9% by the co-application of green tea. The present results suggest an in vivo interaction between tea and folic acid with even low concentrations of green and black tea extracts yielding decreased bioavailabilities of folic acid. Copyright © 2008 John Wiley & Sons, Ltd. [source]