Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 2007
Comparative Study Clinical TrialConcentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes.
The influence of CYP2D6 genotype and CYP2D6 inhibitors on enantiomeric plasma levels of tramadol and O-desmethyltramadol as well as response to tramadol was investigated. One hundred and seventy-four patients received one hundred intravenous tramadol 3 mg/kg for postoperative analgesia. Blood samples drawn 30, 90, and 180 min after administration were analyzed for plasma concentrations of the enantiomers (+)-, (-)tramadol and (+)-, (-)O-desmethyltramadol by liquid chromatography-tandem mass spectrometry. ⋯ Comedication with CYP2D6 inhibitors decreased (+) O-desmethyltramadol concentrations (P<0.01). In PMs, non-response rates to tramadol treatment increased fourfold compared with the other genotypes (P<0.001). In conclusion, CYP2D6 genotype determined concentrations of O-desmethyltramadol enantiomers and influenced efficacy of tramadol treatment.
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Clin. Pharmacol. Ther. · Jun 2007
Multicenter StudyGanciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation.
Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. ⋯ Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.
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Many patients in pain receive inadequate doses of opioids. Fear of government action against prescribing doctors is one cause of this inadequate treatment. The purpose of the study was to assess criminal prosecutions by reviewing press reports of indictments or trials of doctors for opioid offenses during 2 years. ⋯ None were found guilty of murder. Prosecutorial excesses and hyperbole were common. The state medical board's review of appropriateness of prescribing opioids when a doctor-patient relationship is presumed to exist could decrease inappropriate criminal indictments and reduce this component of fear of prescribing adequate opioid therapy for patients in pain.
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Clin. Pharmacol. Ther. · Jun 2007
CommentThe DEA's Balancing Act to Ensure Public Health and Safety.
In their article in this issue, Reidenberg and Willis assert that there are multiple barriers to the adequate treatment of pain and that one of these barriers is fear of government action against a physician who prescribes opioids for patients in pain.(1) At the same time, the authors state that the risk of a physician's being punished by either a state medical board or the Drug Enforcement Administration (DEA) for a patient in pain with adequate medical record documentation is very small.
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Clin. Pharmacol. Ther. · Jun 2007
CommentCan state medical boards adequately respond to reports that physicians are inappropriately prescribing opioids?
In this issue, Reidenberg and Willis share results of a 2-year study of cases in which physicians were criminally prosecuted for their prescribing of opioids "outside the bounds of proper medical practice."(1) They found that in only two of 32 such cases had a state medical board reviewed the case before indictment. In many of the cases, the authors argue that the prosecutors overreached and that these kinds of cases could be better handled by referral to state medical boards.