Cytochrome P4502D6 （CYP2D6） is an important cytochrome P450 enzyme which catalyzes the metabolism of more than 80 drugs. Many of these drugs have a narrow therapeutic index and the combined use of substrates may res...Cytochrome P4502D6 （CYP2D6） is an important cytochrome P450 enzyme which catalyzes the metabolism of more than 80 drugs. Many of these drugs have a narrow therapeutic index and the combined use of substrates may result in significant pharmacokinetic interactions, leading to substrate accumulation and deleterious drug effects. Since the discovery of the debrisoquine/sparteine oxidation polymorphism in the 1970s, numerous studies have investigated its status in various ethnic groups. Currently more than 70 different alleles have been described. The gene frequency of individual alleles of CYP2D6 shows a marked interethnic difference. For Chinese population, the most common alleles of the CYP2D6 gene are CYP2D6＊1, CYP2D6＊2 and CYP2D6＊10. Thus, it is very important to study the relationship between drug interactions and the genetic polymorphism of CYP2D6.展开更多
Tramadol is an atypical opioid analgesic widely used in small animal practice.This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) o...Tramadol is an atypical opioid analgesic widely used in small animal practice.This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs.Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg,IV) at 7-days interval.The sevoflurane MAC was determined using a tail clamp method in each dog ventilated with positive pressure ventilation.The tramadol administration produced a significant reduction in the sevoflurane MAC by 22.3 ± 12.2% (1.44 ± 0.28% with tramadol versus 1.86 ± 0.29% without tramadol,P =0.010).This MAC reduction had been determined from 122 ± 19 to 180 ± 41 min following the tramadol administration.During this period,the plasma concentrations of tramadol and its metabolite,O-desmethyltramadol (M1),decreased from 429 ± 64 to 332 ± 55 ng/mL and from 136 ± 24 to 114 ± 68 ng/mL,respectively,but these changes were not statistically significant (P = 0.070 for tramadol and P = 0.716 for M1).There was no significant difference in heart rate,mean arterial blood pressure and SpO2between the control and tramadol treatment.The dogs that received tramadol treatment sometimes breathed spontaneously.Therefore,their respiratory rates significantly increased and PETCO2decreased during the MAC determination.In conclusion,the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dog.展开更多
基金This work was supported by a grant from the state 863 High Technology Project of China (No. 2004AA2Z3765).
文摘Cytochrome P4502D6 （CYP2D6） is an important cytochrome P450 enzyme which catalyzes the metabolism of more than 80 drugs. Many of these drugs have a narrow therapeutic index and the combined use of substrates may result in significant pharmacokinetic interactions, leading to substrate accumulation and deleterious drug effects. Since the discovery of the debrisoquine/sparteine oxidation polymorphism in the 1970s, numerous studies have investigated its status in various ethnic groups. Currently more than 70 different alleles have been described. The gene frequency of individual alleles of CYP2D6 shows a marked interethnic difference. For Chinese population, the most common alleles of the CYP2D6 gene are CYP2D6＊1, CYP2D6＊2 and CYP2D6＊10. Thus, it is very important to study the relationship between drug interactions and the genetic polymorphism of CYP2D6.
文摘Tramadol is an atypical opioid analgesic widely used in small animal practice.This study was designed to determine the effect of a single intravenous (IV) dose of tramadol on the minimum alveolar concentration (MAC) of sevoflurane in dogs.Six beagle dogs were anesthetized twice to determine the sevoflurane MAC with or without an administration of tramadol (4 mg/kg,IV) at 7-days interval.The sevoflurane MAC was determined using a tail clamp method in each dog ventilated with positive pressure ventilation.The tramadol administration produced a significant reduction in the sevoflurane MAC by 22.3 ± 12.2% (1.44 ± 0.28% with tramadol versus 1.86 ± 0.29% without tramadol,P =0.010).This MAC reduction had been determined from 122 ± 19 to 180 ± 41 min following the tramadol administration.During this period,the plasma concentrations of tramadol and its metabolite,O-desmethyltramadol (M1),decreased from 429 ± 64 to 332 ± 55 ng/mL and from 136 ± 24 to 114 ± 68 ng/mL,respectively,but these changes were not statistically significant (P = 0.070 for tramadol and P = 0.716 for M1).There was no significant difference in heart rate,mean arterial blood pressure and SpO2between the control and tramadol treatment.The dogs that received tramadol treatment sometimes breathed spontaneously.Therefore,their respiratory rates significantly increased and PETCO2decreased during the MAC determination.In conclusion,the single IV dose of tramadol produced a significant reduction in the sevoflurane MAC in dog.
