Abstract:
AIMS:To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor GI198745 (dutasteride) to allow for more accurate predictions of GI198745 concentrations after different dosing schedules. METHODS:In this randomized, single-blind, parallel group study, 32 healthy male volunteers received single oral doses of GI198745 ranging from 0.01 to 40 mg. Data were analysed by nonlinear mixed effects modelling using NONMEM where both linear and nonlinear pharmacokinetic models were examined. RESULTS:The time course of GI198745 serum concentrations indicated concentration dependent elimination, with the apparent half-life increasing with dose. Data were best described by a two-compartment model with first order absorption and parallel linear and nonlinear elimination pathways. Drug absorption was rapid, and was followed by a short distribution phase. A high volume of distribution (511 l) and a low linear clearance (0.58 l h(-1)) combined to give a half-life of up to 5 (1-7) weeks at high concentrations. As concentrations declined towards Km (0.96 ng ml(-1)), the proportion eliminated by the relatively rapid saturable elimination pathway, with a maximum clearance of 6.2 l h(-1), increased and the half-life reduced to about 3 days. The estimated inter individual variability for the linear clearance was high (CV = 70%). CONCLUSIONS:G1198745 pharmacokinetics are well described by a pharmacokinetic model with parallel linear and nonlinear elimination. Simulations using this model show that at daily doses of 0.1 mg the steady state drug concentrations, and the rate at which these are achieved, are mainly influenced by the nonlinear pathway, while at daily doses above 1 mg they are almost entirely influenced by the linear pathway.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Gisleskog PO,Hermann D,Hammarlund-Udenaes M,Karlsson MOdoi
10.1046/j.1365-2125.1999.00843.xkeywords:
subject
Has Abstractpub_date
1999-01-01 00:00:00pages
53-8issue
1eissn
0306-5251issn
1365-2125journal_volume
47pub_type
临床试验,杂志文章,随机对照试验abstract:AIMS:Rifampicin profoundly reduces lopinavir concentrations. Doubled doses of lopinavir/ritonavir compensate for the effect of rifampicin in adults, but fail to provide adequate lopinavir concentrations in young children on rifampicin-based antituberculosis therapy. The objective of this study was to develop a populati...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12101
更新日期:2013-11-01 00:00:00
abstract::1 Roth et al. (1972) have proposed that within the affective disorders there are two distinct syndromes--anxiety and depression--differentiated by the relative predominance of these symptoms, the presence or absence of premorbid maladaptive traits, and the natural outcome of the disorder. 2 Goldberg (1982) on the othe...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb05859.x
更新日期:1983-01-01 00:00:00
abstract:AIM:Drug-induced liver injury (DILI) is often responsible for acute liver failure, drug withdrawal, boxed warnings or drug non-approval. Therefore, we conducted a case-control study to determine the hepatotoxic risk of a wide range of drugs. METHODS:The Berlin Case-Control Surveillance Study FAKOS included all 51 Berl...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12565
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abstract::Serum and milk concentrations of aztreonam were studied in 12 lactating, healthy subjects over the 8 h period after the administration of a single intramuscular or intravenous 1 g dose. Milk concentrations of aztreonam were found to be much lower than serum concentrations at all time points after both routes of inject...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02677.x
更新日期:1985-04-01 00:00:00
abstract:AIMS:Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sou...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14132
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abstract::1 In a preliminary double-blind trial the effects of ephedrine and pseudoephedrine on the blood pressure and heart rate of resting healthy volunteers were compared. Ephedrine 60 or 90 mg were required to raise the diastolic blood pressure above 90 mmHg, whereas 210 or 240 mg pseudoephedrine were required to produce th...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1978.tb04588.x
更新日期:1978-09-01 00:00:00
abstract::1. Six healthy volunteers received single doses of either nomifensine 100 mg, nomifensine 50 mg or placebo at weekly intervals in a randomized double-blind crossover study. 2. Subjects were subjected to a simulated test of car driving at night. 3. Testing lasted about 1.5 h and consisted of measuring responses to ligh...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1977.tb05748.x
更新日期:1977-01-01 00:00:00
abstract::The effects of separate 7 day pretreatments with sulphinpyrazone (800 mg daily) and cimetidine (1 g daily) on the disposition of (+/-)-verapamil have been examined in eight healthy volunteers (four male, four female). Each subject received single oral (80 mg) and intravenous (0.15 mg/kg) doses of verapamil on differen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02658.x
更新日期:1985-03-01 00:00:00
abstract:AIMS:Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxicat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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abstract:AIMS:Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive ther...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12389
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journal_title:British journal of clinical pharmacology
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doi:10.1111/bcp.13360
更新日期:2017-11-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1999.00917.x
更新日期:1999-04-01 00:00:00
abstract::1 Aspirin is partly hydrolyzed to salicylic acid during absorption. Absorbed aspirin is rapidly hydrolyzed systemically. Salicylic acid elimination kinetics are dependent on drug concentration due to the limited capacity of two major biotransformation pathways: formation of salicyluric acid and of salicylphenolic gluc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01811.x
更新日期:1980-10-01 00:00:00
abstract:AIMS:There are no specific criteria for a step-down or withdrawal dose of omalizumab (OMA). Our purpose was to evaluate the viability of a protocol for OMAlizumab DOse REduction (the OMADORE study) in severe allergic asthma (SAA). METHODS:The study population included 35 SAA patients treated during a minimum period of...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13453
更新日期:2018-02-01 00:00:00
abstract::The effects of high and low urine flow rates on the urinary metabolic ratios for paracetamol glucuronidation, sulphation and oxidation were determined at steady-state in seven healthy young adult volunteers. Metabolic partial clearances were unaffected by urine flow rate, but individual paracetamol metabolic ratios va...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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abstract:AIM:Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS:A literature s...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2009.03433.x
更新日期:2009-09-01 00:00:00
abstract:AIMS:To compare the disposition of fluoxetine and norfluoxetine enantiomers in the mother, foetus and infant. METHODS:Blood from pregnant women taking fluoxetine (n = 9), during pregnancy was sampled in the third trimester and at delivery (maternal and cord venous blood), and from the infants 48 h after delivery. The ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2005.02538.x
更新日期:2006-02-01 00:00:00
abstract::1 The haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood p...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::1. Lisinopril and enalapril were administered as 2.5 mg single doses and as eight single daily 2.5 mg doses to separate groups of six patients with chronic renal failure. Patients were receiving regular haemodialysis. 2. In the absence of haemodialysis, the decline in plasma concentrations of lisinopril and enalaprila...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb05319.x
更新日期:1988-12-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1975-02-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.2000.00250.x
更新日期:2000-09-01 00:00:00
abstract::Imagine a medicine that is expected to have very limited effects based upon knowledge of its pharmacology and (patho)physiology and that is studied in the wrong population, with low-quality studies that use a surrogate end-point that relates to the clinical end-point in a partial manner at most. Such a medicine would ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
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更新日期:2013-06-01 00:00:00
abstract::Serum creatinine and drug concentrations were measured at 0, 1, 2, 3, 6, 9 and 12 months in 30 consecutive patients started on amiodarone. In 28 of these patients with no obvious cause for altered renal function, mean serum creatinine increased to 11% above baseline (P < 0.005). Rising creatinine concentrations correl...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb04207.x
更新日期:1993-08-01 00:00:00
abstract::1. Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension. 2. The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and un...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1996-07-01 00:00:00
abstract:AIMS:This study investigates paediatric drug dosage guidelines with the aim of investigating their agreement with body surface area (BSA) scaling principles. METHODS:A total of 454 drug dosage guidelines listed in the AMH-CDC 2015 were examined. Data extracted included the administration, frequency and dose per age br...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13511
更新日期:2018-05-01 00:00:00
abstract::Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001)....
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05582.x
更新日期:1991-05-01 00:00:00
abstract:AIMS:The administration of omeprazole may interfere with the absorption of orally administered drugs by reducing gastric pH and hence tablet dissolution. The aim of this study was to investigate the effects of a 5 day administration of omeprazole on the pharmacokinetics of furazolidone. METHODS:Eighteen healthy (nine ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.0306-5251.2001.01435.x
更新日期:2001-08-01 00:00:00
abstract::1 Five normal subjects received pre-treatment with cimetidine 200 mg three times daily and 400 mg at night for 6 days, or matching placebo. 2 Caffeine (300 mg) was given orally before any treatment and at the beginning of the last day of each treatment course. Treatments were randomly allocated and separated by at lea...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1981.tb01194.x
更新日期:1981-08-01 00:00:00
abstract:PURPOSE:Prescribed daily dose (PDD), the number of doses prescribed to be taken per day, is used to calculate medication adherence using pharmacy claims data. PDD can be substituted by (i) one dose per day (1DD), (ii) an estimate based on the 75th percentile of days taken by patients to refill a script (PDD75 ) or (iii...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14468
更新日期:2020-07-08 00:00:00
abstract:AIMS:Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS:Human liver microsomal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.t01-1-00605.x
更新日期:1997-11-01 00:00:00