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
ReviewAnticipating clinical integration of pharmacogenetic treatment strategies for addiction: are primary care physicians ready?
Emerging pharmacogenomics research on addiction to nicotine, alcohol, cocaine, and opiates may soon lead to improved clinical outcomes by tailoring the type, dose and duration of treatment to individual patients' genotypes. To realize the potential of pharmacogenomics in reducing the burden of addiction, several challenges related to clinical integration of novel treatment strategies will need to be addressed concomitantly with ongoing empirical research. These challenges include the preparedness of primary care physicians (PCPs) to incorporate pharmacogenetics into clinical practice, patients' willingness to undergo genetic testing, the resources and infrastructure needed to deliver such services, adequate financing and reimbursement of pharmacogenetic testing, and privacy and antidiscrimination protections sufficient to reassure physicians and patients that genetic testing will not lead to stigmatization and discrimination.