Journal of Clinical Pharmacology
1552-4604
0091-2700
Mỹ
Cơ quản chủ quản: WILEY , Wiley-Blackwell
Lĩnh vực:
Pharmacology (medical)Pharmacology
Phân tích ảnh hưởng
Thông tin về tạp chí
The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.
Các bài báo tiêu biểu
Comparative Pharmacokinetics of Lovastatin Extended‐Release Tablets and Lovastatin Immediate‐Release Tablets in Humans The pharmacokinetics of lovastatin and its active metabolite lovastatin acid was evaluated in 9 healthy subjects in a three‐period crossover study following a single oral dose of lovastatin extended‐release (ER) tablets and lovastatin immediate‐release (IR) tablets. Participants were dosed with lovastatin IR 40 mg tablets following a standard breakfast, lovastatin ER 40 mg tablets following a standard breakfast, and lovastatin ER 40 mg tablets under fasting conditions. Serial plasma samples were collected for up to 48 hours postdose and assayed for lovastatin and lovastatin acid using a liquid chromatography/mass spectroscopy/mass spectroscopy method. Lovastatin ER tablets, unlike lovastatin IR tablets, exhibited delayed‐ and extended‐release characteristics. The relative bioavailabilitv, in terms of area under the curve values, of lovastatin (156%) and lovastatin acid (124%) was greater from lovastatin ER tablets as compared with lovastatin IR tablets when given with breakfast. An even greater increase in the bioavailability of lovastatin (261%) and lovastatin acid (231%) was observed when the lovastatin ER tablets were administered under fasting conditions. Thus, greater gastrointestinal tract drug absorption of lovastatin from lovastatin ER tablets was demonstrated. Ingestion of a standard breakfast prior to administration of lovastatin ER tablets decreased absorption of lovastatin by approximately 40%, relative to lovastatin ER tablets under fasting conditions.
Tập 42 Số 2 - Trang 198-204 - 2002
Pregnancy Outcome Following Exposure to Topical Retinoids: A Multicenter Prospective Study Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first‐trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8–2.7]), minor birth defects (1.3 [0.4–3.7]), and major birth defects (1.8 [0.6–5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3‐fold (3.4 [1.5–7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.
Tập 52 Số 12 - Trang 1844-1851 - 2012
Isotretinoin Embryopathy—A Continuing Problem First trimester exposure to isotretinoin is associated with an estimated 20% risk of major fetal malformations. Product labeling in force up to August 1988 included a statement that the drug is contraindicated in pregnancy and suggested procedures for prescribing physicians to follow to prevent inadvertent first trimester exposure to the product. This limited educational intervention did not prevent the continued occurrence of isotretinoin‐related birth defects. The effectiveness of recent changes in the package labeling in preventing such birth defects remains to he demonstrated. Two infants with major birth defects associated with first trimester exposure to isotretinoin (Accutane, Roche Laboratories**) were reported to the New Jersey Birth Defects Registry within 6 months. Stimulated by these reports, we sought additional cases in New Jersey and found three. We here describe these five cases of isotretinoin embryopathy, including available information on the circumstances which led to maternal use of isotretinoin during the first trimester of pregnancy. In response to a preliminary report of these cases1 and to investigations by epidemiologists at the U.S. Food and Drug Administration (FDA), the manufacturer altered the package labeling.2 The revised product information includes a more prominent “contraindication and warning” section and a new “patient information/consent” section. The effectiveness of this educational intervention should be evaluated.
Tập 29 Số 5 - Trang 463-465 - 1989
Pharmacokinetics and Safety of Ginsenoside Rd Following a Single or Multiple Intravenous Dose in Healthy Chinese Volunteers The pharmacokinetics and safety of ginsenoside Rd (Rd) were assessed in healthy Chinese volunteers. In the single‐dose study, a randomized, open‐label, 3‐way crossover design was used. Participants were assigned to receive 10, 45, or 75 mg Rd by intravenous infusion, with a 2‐week washout period between dosing periods. Plasma levels of Rd were found to be proportional to dose, with the mean Cmax and AUC0‐∞ ranging from 2.8 to 19.3 mg/L and 27.9 to 212.5 mg·h/L over the dose range studied. Ginsenoside Rd was slowly cleared from plasma (t1/2Z = 17.7–19.3 hours). In the multiple‐dose study, 10 mg Rd was administered once daily for 6 days. Slight drug accumulation was noted. The mean steady‐state Cmax , AUC0‐∞ , and AUCss were 4.0 mg/L, 51.7 mg·h/L, and 26.4 mg·h/L, respectively. The t1/2Z was 20.5 hours, which was similar to the single‐dose value. Ginsenoside Rd was well tolerated with no pattern of dose‐related adverse events. It had a favorable pharmacokinetic and safety profile that enables the drug to be explored in future clinical studies that target patients with acute ischemic stroke.
Tập 50 Số 3 - Trang 285-292 - 2010
Effects of the Oral, Direct Factor Xa Inhibitor Rivaroxaban on Platelet‐Induced Thrombin Generation and Prothrombinase Activity<sup>1</sup> Rivaroxaban (BAY 59‐7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo‐controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5‐ or 30‐mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase‐induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase‐induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen‐induced endogenous thrombin potential was reduced by ∼80% and ∼90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor‐induced endogenous thrombin potential was reduced by ∼40% (5 mg) and ∼65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase‐induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet‐induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma.
Tập 47 Số 11 - Trang 1398-1407 - 2007
The Treatment of Severe Raynaud's Phenomenon with Verapamil Abstract: Verapamil was evaluated in 16 patients with severe Raynaud's phenomenon. Fifty per cent of patients experienced subjective improvement by history, but only one patient had a substantial reduction in the frequency of Raynaud's phenomenon as assessed by diary analysis. We conclude that verapamil is not effective in most patients with severe Raynaud's phenomenon.
Tập 22 Số 1 - Trang 74-76 - 1982
Pharmacokinetics of 2‘,3’‐Dideoxycytidine in Patients with AIDS and Related Disorders The clinical pharmacokinetics of 2′,3′‐dideoxycytidine (DDC) were determined after oral and intravenous administration in ten patients with AIDS or AIDS‐related complex. A high performance liquid chromatography (HPLC) analysis procedure using cation exchange extraction columns was used to measure DDC levels as low as 0.1 μM (21 ng/mL) in plasma and urine. The kinetics of DDC were linear over the dose range of 0.03 to 0.5 mg/kg. Total body clearance was 227 mL/min/m2 and did not change after 6 to 14 days of dosing. The volume of distribution at steady state was 0.54 L/kg. Plasma half‐life was 1.2 hours, and bioavailability was 88%. Most (75%) of the parent drug was found unchanged in the urine. As a result, renal function could play a role in dose adjustment of DDC. Comparison is made between the kinetics of DDC and 3′‐azido‐2′,3′‐dideoxythymidine (AZT). Similarities are noted in half‐life and bioavailability. However, differences are observed for total body clearance, cerebrospinal fluid penetration, volume of distribution, metabolism, and recovery in urine.
Tập 28 Số 9 - Trang 837-842 - 1988
Safety and Efficacy of Chronic Therapy with Captopril in Hypertensive Patients: An Update Abstract: Captopril, an orally active angiotensin‐converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long‐term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin‐angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.
Tập 21 Số 11 - Trang 508-516 - 1981
Relationship Between Gallamine Plasma Concentration and Neuromuscular Paralysis in Surgical Patients Abstract: The pharmacodynamics of the neuromuscular blocking drug gallamine were investigated in 10 surgical patients using a constant‐rate infusion regimen, and results are compared to those for d ‐tubocurarine (dTc). Gallamine effect (paralysis)–time data gathered during and following the infusion were fitted to a pharmacodynamic effect model, while paralysis—plasma concentration data gathered during (onset) and following (offset) the infusion were fitted separately to a nonlinear form of the Hill equation. The effect model was most appropriate in characterizing the combined (on and off infusion) effect data. While there was also an excellent characterization of onset and offset data with the Hill equation, the two effect—concentration curves were not superimposable. The mean (± S.D.) plasma concentration of gallamine at 50 per cent paralysis during onset of action (Cp50(onset) 8.0 ± 1.8 μg/ml) was significantly higher (P < 0.001) than that noted during offset of action (Cp50(offset) 5.4 ± 1.1 μg/ml) or that predicted to exist at steady state using the effect model (Cp50(ss) 5.4 ± 1.4 μg/ml). Cp50(offset) and Cp50(ss) did not differ significantly, and there was no significant difference in the power factor (γ) estimates for the various model fits. Comparison of the pharmacodynamic parameters for gallamine and dTc using the effect model revealed no significant differences in keo , t½ (keo ), and γ estimates. However, Cp50(ss) for gallamine (5.4 ± 1.4 μg/ml) was nine times higher than that for dTc (0.61 ± 0.15 μg/ml) in absolute terms and seven times higher when compared on a molar basis.
Tập 23 Số 5-6 - Trang 243-251 - 1983