Abstract:
PURPOSE:this study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonist used in the treatment of moderate to severe pain. METHODS:a randomized crossover study design with three phases at intervals of 4 weeks was conducted in 12 healthy volunteers. Ritonavir 300 mg, lopinavir/ritonavir 400/100 mg, or placebo b.i.d. for 4 days was given to the subjects. On day 3, 10 mg oxycodone hydrochloride was administered orally. Plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined for 48 h. Pharmacokinetic parameters were calculated with standard noncompartmental methods. Behavioral effects and experimental cold pain analgesia were assessed for 12 h. ANOVA for repeated measures was used for statistical analysis. RESULTS:ritonavir and lopinavir/ritonavir increased the area under the plasma concentration-time curve of oral oxycodone by 3.0-fold (range 1.9- to 4.3-fold; P <0.001) and 2.6-fold (range 1.9- to 3.3-fold; P <0.001). The mean (± SD) elimination half-life increased after ritonavir and lopinavir/ritonavir from 3.6 ± 0.6 to 5.6 ± 0.9 h (P <0.001) and 5.7 ± 0.9 h (P <0.001), respectively. Both ritonavir (P <0.001) and lopinavir/ritonavir (P <0.05) increased the self-reported drug effect of oxycodone. CONCLUSIONS:ritonavir and lopinavir/ritonavir greatly increase the plasma concentrations of oral oxycodone in healthy volunteers and enhance its effect. When oxycodone is used clinically in patients during ritonavir and lopinavir/ritonavir treatment, reductions in oxycodone dose may be needed to avoid opioid-related adverse effects.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Nieminen TH,Hagelberg NM,Saari TI,Neuvonen M,Neuvonen PJ,Laine K,Olkkola KTdoi
10.1007/s00228-010-0879-1subject
Has Abstractpub_date
2010-10-01 00:00:00pages
977-85issue
10eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章,随机对照试验abstract:PURPOSE:The aim of this study is to validate medication proxies for the identification of children diagnosed with atopic disorders that can be applied in various types of epidemiological research. METHODS:Records of 7439 children, aged between 0 and 10 years, in the period 2001 until 2010, were retrieved from the Regi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1940-x
更新日期:2016-01-01 00:00:00
abstract::The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558077
更新日期:1989-01-01 00:00:00
abstract::The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diure...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00541464
更新日期:1986-01-01 00:00:00
abstract::The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following va...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561065
更新日期:1977-12-28 00:00:00
abstract::Thirty patients suffering from essential hypertension were treated successively with placebo, hydralazine alone, and pindolol (Visken) combined with hydralazine. Hydralazine caused a statistically significant reduction in blood pressure and an increase in pulse rate as compared with the placebo: palpitations were an i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614002
更新日期:1975-12-19 00:00:00
abstract::The influence of time of drug administration on pharmacokinetics of theophylline was studied both after ingestion of a sustained-release tablet, containing choline theophyllinate ( Zy 15061-S. R.; Teovent ; Sabidal ; ZYMA S.A.) and after intravenous infusion of aminophylline to eight healthy volunteers. Both drugs wer...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00630288
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor, is indicated for chronic heart failure (HF) and reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for HF. Following oral administration, LCZ696 provides systemic exposure to valsartan and ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2072-7
更新日期:2016-09-01 00:00:00
abstract::We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Tri...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00278469
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy. METHODS:We enrolled 100 outpatients initiating chemotherapy in a university center specializing i...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1874-3
更新日期:2015-08-01 00:00:00
abstract::Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00625804
更新日期:1980-04-01 00:00:00
abstract::The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functio...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00567119
更新日期:1975-04-04 00:00:00
abstract::In a double-blind, randomized study, the long-term effects of timolol and placebo on FEV1, PEFR, FVC, VC, respiratory rate and heart rate were compared in 32 patients surviving acute myocardial infarction, 17 on timolol and 15 on placebo. The patients were assessed before and after 1, 3 and 6 months of medication, and...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00635703
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the ef...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-018-2590-6
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVE:Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA). METHODS:In an open pro...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0153-8
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVE:Because of the risk of haemorrhagic disease of the newborn as a result of a deficit in vitamin K, it is generally agreed that newborns should receive vitamin K. However, there is no consensus concerning the route of administration, dose, number of doses, or dose frequency. METHODS:We studied patterns of vita...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050297
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. METHOD:A randomised, double-blind, placebo-controlled, parallel group, single centre stu...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002280050479
更新日期:1998-07-01 00:00:00
abstract::The relation between plasma concentration of theophylline and number of apnea preterm infants was studied in six patients. The apnea frequency was monitored after cessation of theophylline treatment and plotted against the log plasma concentration of theophylline. It was calculated that at an average plasma concentrat...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561480
更新日期:1980-07-01 00:00:00
abstract::A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sampl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542408
更新日期:1986-01-01 00:00:00
abstract::The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of h...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00198307
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abstract::The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
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abstract::A possible pharmacokinetic interaction between theophylline and repirinast has been investigated in asthmatic patients. The kinetics of theophylline was studied in seven adult in-patients given theophylline 400-800 mg b.d. alone and after three weeks of co-administration of repirinast. There was no effect on the kinet...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679789
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abstract::The pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
abstract::The effect of long-term treatment on the absorption and disposition of metoprolol has been evaluated in 8 healthy, non-smoking, elderly individuals (mean age 74.5 years) and in a control group of 8 healthy, young individuals. Two trace doses of [3H]metoprolol were given i.v., first concomitantly with a single oral 50 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544048
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2018-05-01 00:00:00
abstract::The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One pat...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1983-01-01 00:00:00
abstract:PURPOSE:To assess the efficacy of acetylleucine to improve or stop an attack of vertigo and dizziness (vertigo/dizziness). METHODS:Systematic review by 2 independent reviewers. Consultation of the Medline, Cochrane and ClinicalTrials.gov databases until September 2018. Keywords used: Acetylleucine, Tanganil®, Acetyl-D...
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pub_type: 杂志文章,meta分析
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abstract:OBJECTIVE:To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil (PG) to its active antifol triazine metabolite cycloguanil (CG). METHODS:Case control study conducted on the NW border of Thailand; a single dose of PG (4 mg/kg) was administer...
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pub_type: 临床试验,杂志文章
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abstract::The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract::(1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylat...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1978-06-19 00:00:00