Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jun 2008
ReviewIntegrating family medicine and pharmacy to advance primary care therapeutics.
The prevalence of suboptimal prescribing of medications is well documented. Patients are often undertreated or not offered therapeutic treatments that are likely to confer benefit. As a result, drug-related hospital admissions are common and often preventable. ⋯ However, the effect of integrating a pharmacist providing general services into a primary care group has not been extensively studied. The Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics (IMPACT) project was designed to provide a real-world demonstration of the feasibility of integrating the pharmacist into primary care office practice. This article provides a description of the IMPACT project participants; the IMPACT practice model and the concepts incorporated in its development; some initial results from the program evaluation; sustainability of the model; and some reflections on the implementation of the practice model.
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Clin. Pharmacol. Ther. · Jun 2008
Comparative StudyModeling and simulation to support dose selection and clinical development of SC-75416, a selective COX-2 inhibitor for the treatment of acute and chronic pain.
Pharmacokinetic/pharmacodynamic (PK/PD) models were developed and clinical trial simulations were conducted to recommend a study design to test the hypothesis that a dose of SC-75416, a selective cyclooxygenase-2 inhibitor, can be identified that achieves superior pain relief (PR) compared to 400 mg ibuprofen in a post-oral surgery pain model. PK/PD models were developed for SC-75416, rofecoxib, valdecoxib, and ibuprofen relating plasma concentrations to PR scores using a nonlinear logistic-normal model. ⋯ A placebo- and positive-controlled parallel-group post-oral surgery pain study was conducted evaluating placebo, 60, 180, and 360 mg SC-75416 oral solution, and 400 mg ibuprofen. The study results confirmed the hypothesis that 360 mg SC-75416 achieved superior PR relative to 400 mg ibuprofen (DeltaTOTPAR6=3.3, P<0.05) and demonstrated the predictive performance of the PK/PD models.
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Clin. Pharmacol. Ther. · May 2008
Randomized Controlled Trial Comparative StudyAutonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade.
The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and alpha-2 agonist (dexmedetomidine, DEX). Protocol 1: incremental phenylephrine was administered during control and combined GLY-DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2: muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY-DEX. ⋯ Both GLY-DEX and TMP infusion inhibited norepinephrine release (P<0.01 vs control). GLY-DEX inhibited baseline MSNA (P<0.05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control.
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Clin. Pharmacol. Ther. · Apr 2008
Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief.
The pharmacokinetics and pharmacodynamics of morphine are under the control of several polymorphic genes, which can account for part of the observed interindividual variation in pain relief. We focused on two such genes: ABCB1/MDR1, a major determinant of morphine bioavailability, and OPRM1, which encodes for the mu-opioid receptor, the primary site of action for morphine. ⋯ Combining the extreme genotypes of both genes, the association between patient polymorphism and pain relief improved (P<0.00001), allowing the detection of three groups: strong responders, responders, and non-responders, with sensitivity close to 100% and specificity more than 70%. This study provides a good example of the possible clinical use of pharmacogenetics.