Journal of clinical pharmacology
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Randomized Controlled Trial Multicenter Study
Exposure-response analyses of the effects of pregabalin in patients with fibromyalgia using daily pain scores and patient global impression of change.
Data from 4 phase 2/3 studies were pooled to characterize the exposure response of daily pregabalin (150-600 mg) in patients with fibromyalgia using self-assessed daily pain scores (PAIN) and end-of-treatment patient global impression of change (PGIC). The exposure responses of both endpoints were characterized by an Emax model using nonlinear mixed-effects modeling (NONMEM). Drug effect on PAIN relative to placebo was significant with additional maximum effect of 1.51 points on the logit scale and EC50 of 1.54 ng/mL (dose of 174 mg) and a rapid onset (half-life of 11 hours), consistent with the half-life of the drug. ⋯ Drug response in fibromyalgia was dependent on age and sex, with greater PAIN reduction in older patients, in addition to the effect of creatinine clearance, and in females. For PGIC, administration of pregabalin resulted in an increase in the proportion of patients reporting improvement with an ED50 of 228 mg. The analyses support the recommended dose of pregabalin in patients with fibromyalgia of 300 to 450 mg/d.
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Multicenter Study
Trigeminal neuralgia treated with pregabalin in family medicine settings: its effect on pain alleviation and cost reduction.
The purpose of this study is to analyze the effect of pregabalin (PGB) on pain alleviation, use of health care and non-health care resources, and associated costs in patients with trigeminal neuralgia under usual clinical practice in primary care settings. Sixty-five PGB-naïve patients receiving PGB as monotherapy (n = 36, 55%) or combined with other drugs (n = 29, 45%) fulfill criteria for inclusion in a secondary analysis from a 12-week, multicenter, observational prospective study aimed to ascertain the cost of illness in subjects with neuropathic pain. Pain is evaluated using the Short Form McGill Pain Questionnaire. ⋯ PGB significantly reduces pain scores, use of health care resources (ancillary tests and unscheduled medical visits), and number of LWDEs. Additional cost of PGB treatment (+euro 174 +/- 106) is broadly compensated for by a reduction in both health care costs (-euro 621 +/-1211, P < .001) and indirect costs (-euro 1210 +/- 1141, P < .001). It is concluded that PGB as monotherapy or combined with other drugs is effective in pain management in patients with trigeminal neuralgia and reduces the cost of illness.
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Randomized Controlled Trial Multicenter Study
Pharmacokinetics of novel atrial-selective antiarrhythmic agent vernakalant hydrochloride injection (RSD1235): influence of CYP2D6 expression and other factors.
Vernakalant hydrochloride injection (RSD1235) is a relatively atrial-selective antiarrhythmic agent that converts atrial fibrillation rapidly to sinus rhythm. The pharmacokinetics of vernakalant were explored in healthy volunteers and in patients with atrial fibrillation or atrial flutter in 4 clinical studies. Key pharmacokinetic parameters analyzed were the maximum plasma concentration and the area under the plasma concentration-time curve. ⋯ In the subset that received 2 vernakalant infusions, there was little difference in vernakalant maximum plasma concentration or area under the plasma concentration-time curve from the start of the first infusion to 90 minutes between CYP2D6 poor metabolizers and extensive metabolizers or between those who did or did not receive concomitant CYP2D6-inhibitor medications. Gender, age, and renal function did not have a clinically significant influence on the pharmacokinetics of vernakalant. These results suggest that an assessment of CYP2D6 expression may not be needed when vernakalant is administered acutely and intravenously to patients with atrial fibrillation.
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Randomized Controlled Trial Multicenter Study
Repetitive dosing of intravenous levosimendan improves pulmonary hemodynamics in patients with pulmonary hypertension: results of a pilot study.
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Randomized Controlled Trial Multicenter Study
A 12-month, randomized, controlled study to evaluate exposure and cardiovascular risk factors in adult smokers switching from conventional cigarettes to a second-generation electrically heated cigarette smoking system.
This randomized, controlled, forced-switching, open-label, parallel-group study in 97 adult male and female smokers of conventional cigarettes evaluated biomarkers of tobacco smoke exposure and cardiovascular risk factors. After baseline measurements, smokers were either switched to a second-generation electrically heated cigarette smoking system (EHCSS) or continued smoking conventional cigarettes for 12 months. ⋯ There was a rapid and sustained reduction in all biomarkers of exposure after switching to the EHCSS, with statistically significant reductions from baseline in nicotine equivalents (-18%), plasma cotinine (-16%), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (-73%), total 1-hydroxypyrene (-53%), urine mutagenicity (-52%), 4-aminobiphenyl hemoglobin adducts (-43%), carboxyhemoglobin AUC7-23 h (-80%), and 3-hydroxypropylmercapturic acid (-35%). These reductions in exposure in the EHCSS group were associated with statistically significant and pathophysiologically favorable changes in several cardiovascular risk factors, including white blood cell count (-0.78 x 10(3)/microL), hemoglobin (-0.16 g/dL), hematocrit (-0.44%), urine 11-dehydrothromboxane B2 (-374 ng/24 h), and high-density lipoprotein cholesterol (+5 mg/dL).