Multiple-dose phase I trials--normal volunteers or patients? One viewpoint.

abstract：:Meptazinol, m-(3-ethyl-1-methyl-hexahydro-1-H-azepin-3-yl) phenol hydrochloride is a centrally active opioid analgesic with a specificity for the mu-1 receptor. It has been reported to lack many of the side effects commonly observed with morphine and morphinelike drugs in man. The objective of this study was to assess...

journal_title：Journal of clinical pharmacology

authors： Siegel C,Sunshine A,Richman H,Olson NZ,Robissa N,Cordone R,Estrada N,Laska E

更新日期：1989-11-01 00:00:00

abstract：:Although physiologic modeling has not gained the widespread acceptance that was originally projected, it may serve as the basis for future PK/PD modeling approaches. In addition, with more effort applied to developing in vitro and animal-to-human predictions, physiologic modeling may assume a higher position in the ph...

journal_title：Journal of clinical pharmacology

authors： Colburn WA

更新日期：1988-08-01 00:00:00

abstract：:The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/...

journal_title：Journal of clinical pharmacology

authors： Klassen DK,Stout RL,Spilman PS,Whelton A

更新日期：1989-11-01 00:00:00

abstract：:The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to...

journal_title：Journal of clinical pharmacology

authors： Zhang X,Lin T,Bertasso A,Evans C,Dorr A,Kolis SJ,Salgo M,Patel I,T20-310\/NV16056 Study Group.

更新日期：2007-04-01 00:00:00

abstract：:In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease. Tolvaptan was initiated as daily morning/afternoon doses of 45/15 mg, and uptitrated weekly to 60/30 mg and 90/30 mg according to pa...

journal_title：Journal of clinical pharmacology

authors： Shoaf SE,Chapman AB,Torres VE,Ouyang J,Czerwiec FS

更新日期：2017-07-01 00:00:00

abstract：:To study the pharmacokinetics of single increasing intravenous doses (40-160 mg) and repeated doses (80 mg for 7 days) of lecithinized superoxide dismutase (PC-SOD) in Japanese volunteers and to compare the pharmacokinetics of PC-SOD between Caucasians and Japanese. The Japanese study consisted of 2 parts: a single-do...

journal_title：Journal of clinical pharmacology

authors： Suzuki J,Broeyer F,Cohen A,Takebe M,Burggraaf J,Mizushima Y

更新日期：2008-02-01 00:00:00

abstract：:A selective thromboxane (TX) synthase inhibitor, CS-518, was orally administered to healthy male Japanese volunteers and the pharmacokinetic and pharmacodynamic properties were investigated. The time profile of drug concentrations in plasma was determined, and the effects of the drug on platelet aggregation in plasma ...

journal_title：Journal of clinical pharmacology

authors： Uematsu T,Nagashima S,Inaba H,Mizuno A,Kosuge K,Nakashima M

更新日期：1994-01-01 00:00:00

abstract：:The time course, dose frequency schedule, and dose-response relationship of the citraturic response to orally administered potassium citrate was examined in 22 normal volunteers and 21 patients with uric acid or calcium nephrolithiasis. The slow-release (wax matrix) preparation of potassium citrate produced a rapid an...

journal_title：Journal of clinical pharmacology

authors： Pak CY,Skurla C,Brinkley L,Sakhaee K

更新日期：1984-01-01 00:00:00

abstract：:This study examined warfarin usage for elderly Medicare beneficiaries with atrial fibrillation (AF) who suffered traumatic brain injury (TBI), hip fracture, or torso injuries. Using the 5% Chronic Condition Data Warehouse administrative claims data, this study included fee-for-service Medicare beneficiaries who had a ...

journal_title：Journal of clinical pharmacology

authors： Liu X,Baumgarten M,Smith G,Gambert S,Gottlieb S,Rattinger G,Albrecht J,Langenberg P,Zuckerman I

更新日期：2015-01-01 00:00:00

abstract：:Lormetazepam, an investigational hypnotic, was evaluated for efficacy and withdrawal phenomena in doses of 0.5, 1.0, 1.5, and 2.0 mg in four separate sleep laboratory protocols, each including four placebo baseline nights, seven drug nights, and three placebo withdrawal nights. A moderate degree of efficacy was shown ...

journal_title：Journal of clinical pharmacology

authors： Kales A,Bixler EO,Soldatos CR,Mitsky DJ,Kales JD

更新日期：1982-11-01 00:00:00

abstract：:Fifteen healthy women participated in a study to determine the effect of multiple doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (35 micrograms ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants received three cycles (21 days each of active drug followed by 7 days without medication) ...

journal_title：Journal of clinical pharmacology

authors： Loi CM,Stern R,Koup JR,Vassos AB,Knowlton P,Sedman AJ

更新日期：1999-04-01 00:00:00

abstract：:A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placeb...

journal_title：Journal of clinical pharmacology

authors： Whelton A,Eff J,Magner DJ

更新日期：1992-09-01 00:00:00

abstract：:Anisotropine methyl bromide, an anticholinergic, 80 mg given orally at 8 P.M., suppresses gastric acid secretion through the night without significant side effects. Thirty patients with endoscopy-proved symptomatic duodenal ulcer disease completed a randomized, double-blind, placebo-controlled trial of nighttime aniso...

journal_title：Journal of clinical pharmacology

authors： Bowers JH,Forbes JA,Freston JW

更新日期：1978-07-01 00:00:00

abstract：:Nintedanib, a triple angiokinase inhibitor, has undergone clinical investigation for the treatment of solid tumors and idiopathic pulmonary fibrosis. Nintedanib (Vargatef® ) plus docetaxel is approved in the EU for the treatment of patients with adenocarcinoma non-small cell lung cancer (NSCLC) after first-line chemot...

journal_title：Journal of clinical pharmacology

authors： Dallinger C,Trommeshauser D,Marzin K,Liesener A,Kaiser R,Stopfer P

更新日期：2016-11-01 00:00:00

abstract：:The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively inactive metabolite, has been demonstrated to occur on exposure to gastric acidity in humans. However, the effect of gastric metabolism on the pharmacodynamics of pravastatin has not been studied. In addition, it was hypothesized that so...

journal_title：Journal of clinical pharmacology

authors： Ito MK

更新日期：1998-04-01 00:00:00

abstract：:This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/ritonavir 400/100...

journal_title：Journal of clinical pharmacology

authors： Sekar VJ,Spinosa-Guzman S,De Paepe E,De Pauw M,Vangeneugden T,Lefebvre E,Hoetelmans RM

更新日期：2008-01-01 00:00:00

abstract：:Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. T...

journal_title：Journal of clinical pharmacology

authors： Linnik MD,O'Rourke AM,Crowther MA

更新日期：2008-08-01 00:00:00

abstract：:CBER's philosophy partners with the sponsor's philosophy in the development of electronic dossiers. Based on the experience gained from a number of dossiers, CBER has established a standard management paradigm and imaging platform by which the review of radiographs has been facilitated. ...

journal_title：Journal of clinical pharmacology

authors： Fauntleroy M

更新日期：2001-07-01 00:00:00

abstract：:Pharmacokinetic values of cibenzoline, a new, investigational, antiarrhythmic drug, were determined in 13 patients with varying degree of renal impairment, creatinine clearance range between 5 and 53 mL/min. Cibenzoline plasma levels were measured after direct intravenous injection of one single 1 mg/kg dose. The appa...

journal_title：Journal of clinical pharmacology

authors： Canal M,Flouvat B,Aubert P,Guedon J,Prinseau J,Baglin A

更新日期：1985-04-01 00:00:00

abstract：:Understanding how inhibition of cytochrome P4503A (CYP3A) affects the metabolism of a new drug is critical in determining if a clinically relevant drug interaction will occur. Diltiazem interaction studies assess a given compound's sensitivity to moderate CYP3A inhibition. The present study compared the effect differe...

journal_title：Journal of clinical pharmacology

authors： Friedman EJ,Fraser IP,Wang YH,Bergman AJ,Li CC,Larson PJ,Chodakewitz J,Wagner JA,Stoch SA

更新日期：2011-11-01 00:00:00

abstract：:Clinical investigations using isoform-selective probes to phenotype cytochrome P450 activity and interaction studies using isoform-selective inhibitors to determine P450 involvement in drug metabolism assume minimal interday variability in P450 activity. CYP3A4 is the most abundant human P450 isoform and metabolizes a...

journal_title：Journal of clinical pharmacology

authors： Kharasch ED,Jubert C,Senn T,Bowdle TA,Thummel KE

更新日期：1999-07-01 00:00:00

abstract：:Nine patients with resistant hypertension received captopril for 12 months. Five received captopril alone, four required additional therapy. In the former, mean blood pressure fell from 109 +/- 4.2 mm Hg to 84 +/- 7.5 mm Hg (P less than 0.025) after seven days. A rise to 101 +/- 19 mm Hg was noted at six and 12 months...

journal_title：Journal of clinical pharmacology

authors： Sullivan JM,Taylor JC,Patrick DR,Johnson JG,Ratts TE,Muirhead EE

更新日期：1982-10-01 00:00:00

abstract：:Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages ov...

journal_title：Journal of clinical pharmacology

authors： Lathers CM,Schraeder PL,Claycamp HG

更新日期：2003-05-01 00:00:00

abstract：:Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (20...

journal_title：Journal of clinical pharmacology

authors： Buell JC,Eliot RS,Plachetka JR,Little MR

更新日期：1988-04-01 00:00:00

abstract：:The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on t...

journal_title：Journal of clinical pharmacology

authors： Matzke GR,Frye RF,Alexander AC,Reynolds R,Dixon R,Johnston J,Rault RM

更新日期：1996-02-01 00:00:00

abstract：:This study was undertaken to assess the bioequivalence between a new formulation of propofol 2% and the commercially available product Diprivan. Secondary objectives were to compare the times to onset of and emergence from hypnosis, the hemodynamic effects, and the safety profiles. Twelve healthy male volunteers were ...

journal_title：Journal of clinical pharmacology

authors： Abad-Santos F,Gálvez-Múgica MA,Santos MA,Novalbos J,Gallego-Sandín S,Méndez P,Casimiro C,Gilsanz F

更新日期：2003-04-01 00:00:00

abstract：:R(+)-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha-lipoic acid/dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic p...

journal_title：Journal of clinical pharmacology

authors： Teichert J,Hermann R,Ruus P,Preiss R

更新日期：2003-11-01 00:00:00

abstract：:A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group an...

journal_title：Journal of clinical pharmacology

authors： Kurland AA,Nagaraju A

更新日期：1981-01-01 00:00:00

abstract：:Glasdegib is approved for treating acute myeloid leukemia in elderly patients at 100 mg once daily in combination with low-dose cytarabine. Exposure-efficacy analysis showed that the survival benefit of glasdegib was not glasdegib exposure-dependent. The relationship between glasdegib exposure and adverse event (AE) c...

journal_title：Journal of clinical pharmacology

authors： Ruiz-Garcia A,Shaik N,Lin S,Jamieson C,Heuser M,Chan G

更新日期：2021-03-01 00:00:00

abstract：:The study was undertaken to develop a pharmacokinetic-pharmacodynamic model to characterize efavirenz-induced neuropsychologic impairment, given preexistent impairment, which can be used for the optimization of efavirenz therapy via Monte Carlo simulations. The modeling was performed with NONMEM 7.2. A 1-compartment p...

journal_title：Journal of clinical pharmacology

authors： Bisaso KR,Mukonzo JK,Ette EI

更新日期：2015-11-01 00:00:00