Abstract:
:1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive treatments, each patient under fasting conditions received four of the following five treatments: 200 mg didanosine as a single agent; 200 mg trimethoprim + 1000 mg sulphamethoxazole; 200 mg trimethoprim + 200 mg didanosine; 1000 mg sulphamethoxazole + 200 mg of didanosine and; 200 mg trimethoprim + 1000 mg sulphamethoxazole + 200 mg didanosine. 3. Serial blood and urine samples were collected following the administration of each treatment. Plasma and urine samples were analyzed using high-pressure liquid chromatography (h.p.l.c.)/ultraviolet assays specific for unchanged didanosine, trimethoprim and/or sulphamethoxazole. 4. Percent urinary recovery (%UR) and renal clearance (CLR) emerged as consistently affected parameters, being decreased in the case of didanosine (35%, P = 0.016) and trimethoprim (32%, P = 0.019) and increased in the case of sulphamethoxazole (39%, P = 0.079), when all three agents were coadministered. The magnitude of the changes in didanosine CLR and %UR values was no greater when both trimethoprim and sulphamethoxazole were coadministered vs when each single agent was given with didanosine, suggesting that any effect was not additive. 5. Other key parameters such as Cmax, AUC, and t1/2 for didanosine (1309.9 ng ml-1, 1796.9 ng ml-1 h, and 1.61 h, respectively), trimethoprim (1.96 micrograms ml-1, 22.86 micrograms ml-1 h, and 9.03 h, respectively) or sulphamethoxazole (58.62 micrograms ml-1, 799.7 micrograms ml-1 h and 9.84 h, respectively) were not affected when didanosine was coadministered with either trimethoprim (didanosine: 1751.9 ng ml-1, 2158.0 ng ml-1 h, and 1.28 h; trimethoprim: 1.81 micrograms ml-1, 28.89 micrograms ml-1 h, and 11.4 h), sulphamethoxazole (didanosine: 1279.3 ng ml-1, 1793.2 ng ml-1 h, and 1.61 h; sulphamethoxazole: 53.57 micrograms ml-1, 732.1 micrograms ml-1 h, and 8.95 h), or the combination of trimethoprim and sulphamethoxazole (didanosine: 1283.7 ng ml-1, 1941.8 ng ml-1 h, and 1.38 h; trimethoprim: 1.59 micrograms ml-1, 26.68 micrograms ml-1 h, and 11.3 h; sulphamethoxazole: 59.48 micrograms ml-1, 760.9 micrograms ml-1 h, and 9.47 h). 6. Because the observed differences in CLR and %UR are small and not considered to be clinically relevant, it is not necessary to alter the dosing regimens of didanosine, trimethoprim or sulphamethoxazole when administered in combination to HIV seropositive patients.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Srinivas NR,Knupp CA,Batteiger B,Smith RA,Barbhaiya RHdoi
10.1111/j.1365-2125.1996.tb00184.xsubject
Has Abstractpub_date
1996-03-01 00:00:00pages
207-15issue
3eissn
0306-5251issn
1365-2125journal_volume
41pub_type
临床试验,杂志文章,随机对照试验abstract:AIMS:In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N-demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N-demethylation of IMI. METHODS:Healthy subjects were given troleando...
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.1365-2125.1997.00649.x
更新日期:1997-08-01 00:00:00
abstract::We have introduced to the course in pharmacology for medical students a simple human experiment that demonstrates the efficacy of activated charcoal in gastrointestinal drug binding. Sixty-one students were given 40 mg frusemide with water, water only, or 40 mg frusemide and 8 g activated charcoal with water either im...
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.1365-2125.1990.tb03805.x
更新日期:1990-09-01 00:00:00
abstract::1 The protein binding of seven non-steroidal anti-inflammatory drugs (indomethacin, tolmetin, salicylic acid, ibuprofen, flurbiprofen, naproxen and GP53,633) and warfarin was investigated by equilibrium dialysis in simultaneous samples of synovial fluid and plasma from 12 arthritic patients. 2 The protein binding of a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb01469.x
更新日期:1983-01-01 00:00:00
abstract:AIMS:To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS:Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00068.x
更新日期:1999-11-01 00:00:00
abstract::1 Analgesic nephropathy is part of the analgesic syndrome which has gastrointestinal, haematological, cardiovascular, psychological and psychiatric, and pregnancy and gonadal manifestations; premature ageing may also be a feature. 2 Analgesic nephropathy is a form of renal disease characterized by renal papillary necr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1980.tb01824.x
更新日期:1980-10-01 00:00:00
abstract::There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of ca...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12603
更新日期:2015-07-01 00:00:00
abstract::The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therap...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2002.01623.x
更新日期:2002-07-01 00:00:00
abstract:AIMS:Voriconazole is a novel triazole with broad-spectrum antifungal activity. It is likely that some patients receiving voriconazole may also require treatment with the anticoagulant warfarin. Cytochrome P450 isoenzymes are important in the metabolism of both these drugs. This study investigated the effect of voricona...
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.1365-2125.2003.01995.x
更新日期:2003-12-01 00:00:00
abstract:AIM:α1 -Acid glycoprotein (AAG), which is a major binding protein of docetaxel, is considered to be a determinant for docetaxel pharmacokinetics. However, there are no reports about the impact of serum AAG on pharmacokinetics and pharmacodynamics in elderly patients treated with docetaxel. The aim of this prospective s...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13354
更新日期:2017-11-01 00:00:00
abstract::The antiarrhythmic effects of verapamil were observed before it was appreciated that it was a calcium ion-antagonist. Intravenous verapamil is highly effective in the termination of paroxysmal reciprocating atrioventricular tachycardia, whether associated with preexcitation or involving the atrioventricular node alone...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1986.tb02869.x
更新日期:1986-01-01 00:00:00
abstract:AIM:We aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam. METHODS:In an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg ora...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12502
更新日期:2015-02-01 00:00:00
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:Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P-gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2-K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this tri...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13609
更新日期:2018-09-01 00:00:00
abstract::Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subseq...
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.1365-2125.1986.tb02929.x
更新日期:1986-11-01 00:00:00
abstract::The effects of a single dose of sulindac 200 mg and placebo on the capsaicin-induced cough reflex were studied in a two-phase double-blind crossover study in 18 healthy subjects. Sulindac increased the threshold for capsaicin cough response significantly, but did not alter D5, peak response, or the total cough respons...
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.1365-2125.1991.tb05518.x
更新日期:1991-02-01 00:00:00
abstract::1. Oxycodone hydrochloride (0.1 mg kg-1) was given by intravenous bolus to 18 children after ophthalmic surgery. Plasma was sampled for up to 8 h. Blood pressure, heart rate, peripheral arteriolar oxygen saturation, end-tidal carbon dioxide and halothane concentrations and ventilatory rate were also recorded. 2. Mean ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04324.x
更新日期:1994-07-01 00:00:00
abstract::1. The primary action of the converting enzyme inhibitors to prevent the formation of angiotensin II can explain a decrease in peripheral vascular resistance in patients with elevated, but not in those with normal or reduced plasma renin levels. 2. The inhibition of the breakdown of bradykinin will potentiate the vaso...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1989.tb03585.x
更新日期:1989-01-01 00:00:00
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract:AIMS:Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. METHODS:Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, histor...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.13936
更新日期:2019-07-01 00:00:00
abstract::1 The effect of pregnancy on the binding of phenytoin and phenobarbitone to serum proteins was studied in normal women and in drug treated epileptic women. 2 The binding of both drugs was reduced during pregnancy. The reduction correlated positively with the gestational age and negatively with the serum albumin concen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01420.x
更新日期:1982-04-01 00:00:00
abstract::Highly active antiretroviral therapy is recommended for HIV-infected pregnant women to prevent mother-to-child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2008.03220.x
更新日期:2008-08-01 00:00:00
abstract:AIMS:To assess the utility of human hepatic microsomes for predicting in vivo intrinsic clearance (CLint ) via the use of four cytochrome P450 2C9 substrates: phenytoin, tolbutamide (S)-ibuprofen (two pathways) and diclofenac, and to examine the role of exogenous albumin within the microsomal incubation. METHODS:V max...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1999.00935.x
更新日期:1999-06-01 00:00:00
abstract::The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment with VGB. After VGB (2-3.5 g day(-1) for a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb00422.x
更新日期:1993-12-01 00:00:00
abstract::The effect of acute migraine attack and rectally given metoclopramide on the absorption of orally given tolfenamic acid (300 mg) was investigated in seven female patients in a crossover study consisting of four phases, two without migraine and two during migraine. Metoclopramide hydrochloride (20 mg) or placebo was gi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb05001.x
更新日期:1984-01-01 00:00:00
abstract:AIMS:To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001; n = 49) and from the pivotal clinical study (Study 1053; n = 74). METHODS:Data from both studies ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14250
更新日期:2020-07-01 00:00:00
abstract::1. Nine healthy volunteers received 10 mg nitrendipine or placebo orally in random order. 2. In the subsequent 5 h urinary sodium excretion was 20% higher after nitrendipine, without any significant difference between the volume of urine excreted after nitrendipine or placebo. Mean blood pressure fell by 5 mm Hg (P le...
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.1365-2125.1990.tb03817.x
更新日期:1990-10-01 00:00:00
abstract::1 Two studies were carried out on acutely psychotic patients receiving chlorpromazine (100 mg) 8-hourly. 2 In the pilot study on five patients, plasma chlorpromazine concentrations fell over the course of 3 weeks of treatment and parallel changes were noted in the plasma half-life of antipyrine, salivation rate and ha...
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.1365-2125.1975.tb01576.x
更新日期:1975-06-01 00:00:00
abstract::1. The absorption of ciprofloxacin from different regions of the human gastrointestinal tract was investigated in four healthy males using a remote-controlled drug delivery device (hf-capsule). 2. Significant differences in AUC were observed in the control study (oral administration of ciprofloxacin solution without t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03740.x
更新日期:1990-07-01 00:00:00
abstract:AIMS:Vancomycin is an important antibiotic for critically ill patients with Gram-positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tool...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14360
更新日期:2020-12-01 00:00:00
abstract::The pharmacokinetics of metoclopramide have been studied in nine children receiving the drug as prophylaxis for cytotoxic induced vomiting. Plasma concentrations of metoclopramide have also been studied in three children with dystonic reactions to the drug. The pharmacokinetics in children were similar to those report...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02090.x
更新日期:1983-05-01 00:00:00