Abstract:
AIMS:Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. METHODS:A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1:2, 1:1, 2:1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. RESULTS:'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PetCO(2) = 55 mmHg (V(E55)) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. CONCLUSIONS:Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Ladd LA,Kam PC,Williams DB,Wright AW,Smith MT,Mather LEdoi
10.1111/j.1365-2125.2005.02368.xkeywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
524-35issue
5eissn
0306-5251issn
1365-2125pii
BCP2368journal_volume
59pub_type
临床试验,杂志文章,随机对照试验abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the int...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04169.x
更新日期:2012-07-01 00:00:00
abstract:AIM:Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS:We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04010.x
更新日期:2011-09-01 00:00:00
abstract:AIMS:BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12941
更新日期:2016-07-01 00:00:00
abstract::Twelve patients with acute uncomplicated falciparum malaria were admitted to the Hospital for Tropical Diseases for 42 days. The patients were treated with halofantrine 500 mg 6 hourly for three doses and halofantrine and its desbutyl metabolite were analysed in plasma by h.p.l.c. Cmax values of halofantrine and desbu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb05567.x
更新日期:1991-04-01 00:00:00
abstract:AIMS:To evaluate the effect of a 3-day regimen of ibuprofen 600 mg x 4 on acute postoperative swelling and pain and other inflammatory events after third molar surgery compared with a traditional regimen of paracetamol 1000 mg x 4. METHODS:A controlled, randomized, double-blind, cross-over study where 36 patients (26 ...
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.1365-2125.2003.01779.x
更新日期:2003-04-01 00:00:00
abstract::The effects of locally administered physostigmine and di-isopropylphosphorofluoridate (DFP) were compared on the secretory response of sweat glands to intradermally injected acetylcholine and carbachol in healthy male volunteers (physostigmine: six subjects; DFP: one subject). The response to acetylcholine reached its...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05166.x
更新日期:1986-02-01 00:00:00
abstract::1. The relationship between the metabolism of the antiarrhythmic drug mexiletine and the debrisoquine/sparteine-type polymorphism was studied in vitro, using microsomes from six human livers, and in vivo, in nine healthy drug-free volunteers with wide variation in their ability to hydroxylate debrisoquine. 2. There wa...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1991.tb03931.x
更新日期:1991-10-01 00:00:00
abstract::Activation of mu opioid receptors on sensory nerves in the lung represents an attractive mechanism for reducing cough and reflex bronchoconstriction. We have examined the effect of the peptide 443C81, a peripherally acting mu opioid agonist, on the cough and reflex increase in respiratory resistance (Rrs) produced by ...
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.tb03966.x
更新日期:1991-11-01 00:00:00
abstract:AIMS:Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS:DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transport...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13186
更新日期:2017-05-01 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::1. The pharmacokinetics of methylprednisolone (MP) were studied in five normal subjects following intravenous doses of 20, 40 and 80 mg methylprednisolone sodium succinate (MPSS) and an oral dose of 20 mg methylprednisolone as 4 x 5 mg tablets. Plasma concentrations of MP and MPSS were measured by both high performanc...
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.tb05366.x
更新日期:1989-03-01 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
doi:10.1111/j.1365-2125.1992.tb05643.x
更新日期:1992-10-01 00:00:00
abstract::1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1982.tb01870.x
更新日期:1982-06-01 00:00:00
abstract:AIMS:To assess whether frequency of placebo administration is associated with duodenal ulcer healing. METHODS:A systematic literature review of randomized clinical trials was undertaken. 79 of 80 trials that met the inclusion criteria. The pooled 4 week placebo healing rate of all duodenal ulcer trials that employed a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1046/j.1365-2125.1999.00094.x
更新日期:1999-12-01 00:00:00
abstract:AIM:The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. METHODS:Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12971
更新日期:2016-08-01 00:00:00
abstract:AIMS:Although genetic, clinical and demographic factors have been shown to explain approximately half of the inter-individual variability in warfarin dose requirement in adults, less is known about causes of dose variability in children. This study aimed to identify and quantify major genetic, clinical and demographic ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12308
更新日期:2014-07-01 00:00:00
abstract::1. The effect of icatibant (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8] bradykinin) a potent B2-kinin receptor antagonist, was studied on bradykinin-induced vasodilation in the human forearm. 2. Eight healthy normotensive men were studied in a rising dose random-placebo controlled study. Placebo and icatibant (20, 50 and 100 mic...
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.1365-2125.1994.tb04360.x
更新日期:1994-10-01 00:00:00
abstract:AIMS:Previous studies of the prescription patterns of psychotropic medications in patients with schizophrenia have highlighted a high rate of antipsychotic polypharmacy, but data in Asia are sparse. This study seeks to examine the prevalence of antipsychotic polypharmacy in patients with schizophrenia and compare the d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1365-2125.2004.02102.x
更新日期:2004-08-01 00:00:00
abstract::The acute peripheral vascular and diuretic effects of intravenous frusemide 10 mg and 20 mg were compared with those of bumetanide 250 micrograms and 500 micrograms in a group of 10 salt depleted volunteers. Significant reductions in forearm blood flow (FBF) were observed after frusemide 10 mg (-0.77 ml 100 ml-1 min-1...
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.tb05207.x
更新日期:1986-04-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Recently, we have shown that the plasma concentration of R-fexofenadine is greater than that of the S-enantiomer. Although itraconazole co-administration is known to increase the bioavailability of a racemic mixture of fexofenadine, little is known about the stereoselective inhi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2008.03116.x
更新日期:2008-05-01 00:00:00
abstract::1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocyte 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of various groups of patients--those who have not received digoxin, those during the early phases of treatment, those...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb05811.x
更新日期:1979-08-01 00:00:00
abstract:AIMS:To assess whether hepatic impairment influences the pharmacokinetics of ziprasidone. METHODS:Thirty subjects with normal hepatic function or a primary diagnosis of clinically significant cirrhosis (Child-Pugh A or B) were enrolled into an open-label, multicentre, multiple-dose study. The subjects with chronic, st...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1365-2125.2000.00149.x
更新日期:2000-01-01 00:00:00
abstract:AIMS:Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS:The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children aft...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2011.04081.x
更新日期:2012-01-01 00:00:00
abstract::The effects of the proton pump inhibitor lansoprazole on the bioavailability of a low-dose oral contraceptive (OC), containing 0.03 mg ethinyloestradiol (EE) and 0.15 mg levonorgestrel (LNG), were investigated. Twenty-four healthy females (aged 19-35 years; weight 60.6 +/- 7.1 kg) participated in a multiple-dose, plac...
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.1365-2125.1994.tb04370.x
更新日期:1994-10-01 00:00:00
abstract::1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection ev...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1978.tb00838.x
更新日期:1978-08-01 00:00:00
abstract::1 Twelve-week courses of oxprenolol and methyldopa were administered in a randomised, double-blind cross over study to ten insulin dependent hypertensive diabetics. 2 Prior to treatment, and at the end of each period of drug administration, fasting levels of high density lipoprotein, triglycerides, free fatty acids an...
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.1365-2125.1982.tb01360.x
更新日期:1982-02-01 00:00:00
abstract::The pharmacokinetics of piretanide, a new loop diuretic, were studied in four patients with GFR 4.7-14.8 ml/min. An oral dose of piretanide 18 mg was given at 08.00 h in two patients and at 08.00 h and 14.00 h in two. Blood samples were drawn after 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h. Serum concentrations of pireta...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1983.tb01509.x
更新日期:1983-03-01 00:00:00
abstract::1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects rec...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1991.tb05610.x
更新日期:1991-07-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04285.x
更新日期:2012-11-01 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