Abstract：
AIM:Identify and quantify factors describing variability of amikacin clearance in preterm neonates at birth. METHODS:Population pharmacokinetics of amikacin were estimated in a cohort of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24-30 weeks; weight 1.07, SD 0.34, range 0.45-1.98 kg, postnatal age < 72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal anti-inflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis. RESULTS:A one-compartment linear disposition model with zero order input (0.3 h i.v. infusion) and first-order elimination was used. The population parameter estimate for volume of distribution (V) was 40.2 l per 70 kg. Clearance (CL) increased from 0.486 l h(-1) per 70 kg at 24 weeks PCA to 0.940 l h(-1) per 70 kg by 30 weeks PCA. The population parameter variability (PPV) for CL and V was 0.336 and 0.451. The use of a NSAID (either aspirin or ibuprofen) in the first day of life reduced amikacin clearance by 22%. Overall 65% of the variability of CL was predictable. Weight explained 48%, PCA 15% and NSAIDs 2%. CONCLUSIONS:Size and post-conception age are the major contributors to clearance variability in extreme premature neonates (<31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Allegaert K,Anderson BJ,Cossey V,Holford NHdoi
10.1111/j.1365-2125.2005.02530.xkeywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
39-48issue
1eissn
0306-5251issn
1365-2125pii
BCP2530journal_volume
61pub_type
杂志文章abstract：:1. We present a novel index for expressing the exposure of the infant to drugs in breast milk, which unifies two independent factors: a pharmacokinetic parameter, drug clearance, and a physiochemical parameter, i.e. milk-to-maternal plasma drug concentration ratio (M/P ratio). 2. During breast-feeding by a woman recei...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04331.x
更新日期：1994-08-01 00:00:00
abstract：:Integration of clinical and preclinical pharmacology in pharmaceutical companies could be improved by several key recommendations: Companies should ensure that there is an adequate pool of trained clinical pharmacologists and preclinical pharmacologists. Training should include topics that allow clinical pharmacologis...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04239.x
更新日期：2012-06-01 00:00:00
abstract：:1. The aromatic 2-hydroxylation of imipramine was studied in microsomes from three human livers. The kinetics were best described by a biphasic enzyme model. The estimated values of Vmax and Km for the high affinity site ranged from 3.2 to 5.7 nmol mg-1 h-1 and from 25 to 31 microM, respectively. 2. Quinidine was a po...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1992.tb04133.x
更新日期：1992-09-01 00:00:00
abstract：AIMS:The aim of the present study was to determine how the pharmacokinetics of meloxicam are affected by kidney dysfunction and consequently to define the appropriate dose for the use of meloxicam in patients with mild or moderate renal impairment. METHODS:Meloxicam was administered to subjects with mild (creatinine c...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1997.tb00030.x
更新日期：1997-01-01 00:00:00
abstract：:1 To compare the haemodynamic effects of secondary characteristics of beta-adrenoceptor blockers with an angiotensin converting enzyme inhibitor forty patients with previously untreated mild to moderate hypertension were prescribed either atenolol 50-100 mg day-1, labetalol 200-800 mg day-1, pindolol 10-30 mg day-1 or...
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.1365-2125.1987.tb03157.x
更新日期：1987-08-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Variants in the CYP2C9 (i.e. *2 and *3) and VKORC1 (i.e. 1173C/T or -1639G/A) genes have been shown to influence warfarin dose requirements. However, these factors seem to explain less of the dose variability in African Americans who have a lower prevalence of the CYP2C9*2 and *...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03709.x
更新日期：2010-09-01 00:00:00
abstract：:Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:Since platelet activation has been incriminated in the pathogenesis of asthma, we have investigated the effect of one of its major granule-derived mediators, 5-hydroxytryptamine (5-HT, serotonin) on airway calibre in normal (12), atopic non-asthmatic (12) and atopic asthmatic subjects (16). On separate days subjects i...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1986.tb02923.x
更新日期：1986-10-01 00:00:00
abstract：AIMS:The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives. METHODS:Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44...
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.1365-2125.1998.00811.x
更新日期：1998-11-01 00:00:00
abstract：:Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02439.x
更新日期：1984-01-01 00:00:00
abstract：:1 The anticholinergic effects of atropine and two antihistamines (terfenadine and mequitazine) were investigated vs placebo in a double-blind study. 2 Salivary secretion, basal pupil diameter, pilocarpine (0.25%) induced miosis and heart rate were determined in eight healthy volunteers, seven male and one female, aged...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1988.tb03278.x
更新日期：1988-01-01 00:00:00
abstract：AIMS:To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. METHODS:Human liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP an...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1365-2125.2009.03476.x
更新日期：2009-10-01 00:00:00
abstract：:In a dog model of partial myocardial ischaemia, superimposed ST segment elevations in epicardial ECGs were inhibited by nicardipine over a cumulative i.v. dose range of 1-20 micrograms kg-1. Over the cumulative i.v. dose range of 0.5-166.5 micrograms kg-1, nicardipine had little overall effect on gross cardiac conduct...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05142.x
更新日期：1985-01-01 00:00:00
abstract：AIMS:To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. METHODS:Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid ((99m)Tc-...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02835.x
更新日期：2007-06-01 00:00:00
abstract：:1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1979.tb04699.x
更新日期：1979-01-01 00:00:00
abstract：:1. The inhibitory effect of sufotidine, a new histamine H2-receptor antagonist, on gastric secretion of acid and pepsin was studied in six healthy male volunteers. This was a three-way, cross-over, randomized, double-blind study. On each of 3 study days, the drug in a dose of 600 mg, or placebo, was administered eithe...
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.1365-2125.1989.tb03519.x
更新日期：1989-10-01 00:00:00
abstract：AIMS:Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS:T...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1999.00027.x
更新日期：1999-09-01 00:00:00
abstract：AIMS:The protease inhibitor indinavir is characterized by an important interindividual pharmacokinetic variability, which results from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A and the multidrug efflux pump P-glycoprotein (P-gp), encoded by MDR1. Using a population pharmacokinetic approach, we in...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2007.02903.x
更新日期：2007-09-01 00:00:00
abstract：AIMS:To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS:Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inh...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2007.02856.x
更新日期：2007-10-01 00:00:00
abstract：:The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 pa...
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.tb05622.x
更新日期：1991-07-01 00:00:00
abstract：AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2005.02484.x
更新日期：2005-11-01 00:00:00
abstract：:Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute di...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02548.x
更新日期：1984-11-01 00:00:00
abstract：:Doxepin and N-desmethyldoxepin concentrations in plasma and breast milk from a lactating mother and in plasma from her infant were measured during an 8 week period using high performance liquid chromatography. Plasma concentrations ranged from 35-68 microgram l-1 for doxepin and 65-131 microgram l-1 for N-desmethyldox...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05106.x
更新日期：1985-11-01 00:00:00
abstract：:1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. 2. Haem arginate decreased the faecal content of protoporphyrin from 557 +/- 91 to 118 +/- 32 (me...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb05315.x
更新日期：1988-12-01 00:00:00
abstract：:This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2125.2003.01811.x
更新日期：2003-04-01 00:00:00
abstract：:1. The purpose of this study was to determine the effects of cardiac output on distribution and elimination kinetics of the marker compound sorbitol. 2. The disposition kinetics of sorbitol were investigated after rapid intravenous injection and arterial sampling in nine patients who had undergone cardiac catheterizat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.03121.x
更新日期：1996-04-01 00:00:00
abstract：:1 As part of a prospective study on the use of digoxin in a general practice, plasma digoxin concentrations were measured in all patients receiving the drug. 2 A low mean plasma digoxin concentration was observed, suggesting a cautious approach to digitalization. 3 The correlation between plasma digoxin concentration ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1977.tb00720.x
更新日期：1977-06-01 00:00:00
abstract：AIM:To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing. METHODS:Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patie...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14256
更新日期：2020-08-01 00:00:00
abstract：AIMS:Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptive...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.2003.01983.x
更新日期：2004-03-01 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
