M Sandström1, L E Simonsen, A Freijs, M O Karlsson. 1. Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Box 580, SE-751 23 Uppsala, Sweden.
Abstract
PURPOSE: The aim of the present study was to investigate possible pharmacokinetic interactions between epirubicin (EPI) and docetaxel (DTX) in rats. METHODS: Male Sprague Dawley rats (n = 36) were used in the study. They received either DTX (5 mg/kg, n = 9), EPI (3.5 mg/kg, n = 13), or a combination (5 mg/kg + 3.5 mg/kg, n = 14), administered as intravenous bolus doses. Blood samples were collected at various time-points between 3 min and 45 h after dose administration. DTX and EPI plasma concentrations were determined by HPLC analysis. Pharmacokinetic evaluation was carried out using the NONMEM program. RESULTS: A three-compartment model best described the concentration-time profiles for EPI. Clearance (CL), intercompartmental clearances (Q2 and Q3), central (V1) and peripheral (V2 and V3) volumes of distribution were estimated as 3. 57 l/h per kg, 5.01 l/h per kg, 12.48 l/h per kg, 0.805 l/kg, 3.67 l/kg and 158 l/kg, respectively. A two-compartment model was sufficient to describe the DTX data. CL, intercompartmental clearance (Q), V1 and V2 for DTX were estimated as 7.3 l/h per kg, 4. 6 l/h per kg, 0.69 l/kg and 2.6 l/kg, respectively. No significant change in the disposition of either drug was found when they were administered in combination compared to when they were given singly. CONCLUSION: Concurrent treatment with EPI and DTX does not appear to cause any changes in the pharmacokinetics of the drugs in rats.
PURPOSE: The aim of the present study was to investigate possible pharmacokinetic interactions between epirubicin (EPI) and docetaxel (DTX) in rats. METHODS: Male Sprague Dawley rats (n = 36) were used in the study. They received either DTX (5 mg/kg, n = 9), EPI (3.5 mg/kg, n = 13), or a combination (5 mg/kg + 3.5 mg/kg, n = 14), administered as intravenous bolus doses. Blood samples were collected at various time-points between 3 min and 45 h after dose administration. DTX and EPI plasma concentrations were determined by HPLC analysis. Pharmacokinetic evaluation was carried out using the NONMEM program. RESULTS: A three-compartment model best described the concentration-time profiles for EPI. Clearance (CL), intercompartmental clearances (Q2 and Q3), central (V1) and peripheral (V2 and V3) volumes of distribution were estimated as 3. 57 l/h per kg, 5.01 l/h per kg, 12.48 l/h per kg, 0.805 l/kg, 3.67 l/kg and 158 l/kg, respectively. A two-compartment model was sufficient to describe the DTX data. CL, intercompartmental clearance (Q), V1 and V2 for DTX were estimated as 7.3 l/h per kg, 4. 6 l/h per kg, 0.69 l/kg and 2.6 l/kg, respectively. No significant change in the disposition of either drug was found when they were administered in combination compared to when they were given singly. CONCLUSION: Concurrent treatment with EPI and DTX does not appear to cause any changes in the pharmacokinetics of the drugs in rats.
Authors: Kiyohiko Sugano; Manfred Kansy; Per Artursson; Alex Avdeef; Stefanie Bendels; Li Di; Gerhard F Ecker; Bernard Faller; Holger Fischer; Grégori Gerebtzoff; Hans Lennernaes; Frank Senner Journal: Nat Rev Drug Discov Date: 2010-08 Impact factor: 84.694
Authors: Stephan T Stern; Peng Zou; Sarah Skoczen; Sherwin Xie; Barry Liboiron; Troy Harasym; Paul Tardi; Lawrence D Mayer; Scott E McNeil Journal: J Control Release Date: 2013-05-09 Impact factor: 9.776