Abstract:
:The pharmacokinetics of grepafloxacin in healthy male subjects following single oral administration of doses ranging from 200 to 1200 mg, and following repeated oral administration of 400 and 800 mg doses are reported. Plasma levels of grepafloxacin reached a peak within 2 hours (on average) following drug administration and then declined bi-exponentially with concentrations being detectable (> 5 micrograms/L) in the plasma for at least up to 72 hours postdose. The high values for the apparent volume of distribution (5 to 8 L/kg) suggested extensive distribution of grepafloxacin in the tissues. Only a small percentage of the administered dose (ranging from 6% to 9.5%) was recovered in the urine as unchanged grepafloxacin, suggesting that metabolism, rather than urinary excretion, is the major elimination route. The half-life of grepafloxacin was about 12 hours after single doses and about 15 hours after repeat doses. The trough levels increased significantly over the first 3 days of repeat administration; thereafter, the changes were small, with steady-state being reached by the fifth day. The area under the concentration-time curve (AUC24 h) values observed on days 7 and 14 of repeat administration, at each dose level, were similar, suggesting that steady-state is maintained. The area values increased more than proportionally after administration of increasing single and repeat doses, suggesting nonlinear kinetics. The elimination half-life and renal clearance did not change with increasing doses. Saturation in the metabolism of grepafloxacin and possibly in the distribution into a peripheral compartment, as suggested by a decrease in the total plasma clearance and in the apparent volume of distribution, could be the origin of the nonlinear kinetics. However, this deviation from linearity is unlikely to be of clinical significance, since it was very small over the recommended range of therapeutic doses (400 to 600 mg once daily). Compared with other quinolones, grepafloxacin showed the longest half-life and the highest apparent volume of distribution. These features, together with the excellent bactericidal activity of grepafloxacin, support the recommended dosage regimen of grepafloxacin for the treatment of respiratory tract infections and sexually transmitted diseases.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Efthymiopoulos C,Bramer SL,Maroli Adoi
10.2165/00003088-199700331-00003subject
Has Abstractpub_date
1997-01-01 00:00:00pages
1-8eissn
0312-5963issn
1179-1926journal_volume
33 Suppl 1pub_type
临床试验,杂志文章abstract:BACKGROUND AND OBJECTIVE:Oral levodopa-carbidopa (LC-oral) treatment in advanced Parkinson's disease (PD) is associated with motor complications due to large fluctuations in levodopa plasma concentrations. Levodopa-carbidopa intestinal gel (LCIG) provides individualized continuous levodopa-carbidopa delivery through in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0265-3
更新日期:2015-09-01 00:00:00
abstract::Routine use of therapeutic drug monitoring in children is helpful in individualizing the dosage during long term treatment (e.g. theophylline and antiepileptic drugs) and in checking against toxic accumulation of drug in neonates (e.g. digoxin, theophylline/caffeine and aminoglycoside antibiotics). In individual patie...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198900171-00003
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:A simple approach is proposed to predict drug clearance in children when no paediatric data are available for drugs metabolised by cytochromes. METHODS:The maturation functions of cytochrome activity and binding proteins in plasma were combined with several measures of body size to describe dr...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0596-3
更新日期:2018-07-01 00:00:00
abstract::The combination of artemether and lumefantrine (benflumetol) is a new and very well tolerated oral antimalarial drug effective even against multidrug-resistant falciparum malaria. The artemether component is absorbed rapidly and biotransformed to dihydroartemisinin, and both are eliminated with terminal half-lives of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199937020-00002
更新日期:1999-08-01 00:00:00
abstract::Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199631030-00004
更新日期:1996-09-01 00:00:00
abstract::Intraventricular administration of chemotherapy is one approach to overcoming the limited distribution of anticancer drugs and their active metabolites into the CNS. This form of regional chemotherapy has led to effective treatment of occult and overt meningeal leukaemia in humans. In contrast, the efficacy of this th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544010-00001
更新日期:2005-01-01 00:00:00
abstract::The various components required for individualising clinical drug dosage regimens are reviewed, including a study of 3 types of fitting procedures, 2 types of gentamicin pharmacokinetic model and the utility of D-optimal times for obtaining serum gentamicin concentrations. The combination of the current Bayesian fitti...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121060-00006
更新日期:1991-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Veliparib (ABT-888) is a potent oral inhibitor of Poly(ADP-ribose) polymerase enzyme that is currently in development for the treatment of non-hematologic and hematologic malignancies. This analysis characterizes the population pharmacokinetics of veliparib, including developing a structural ph...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-013-0130-1
更新日期:2014-05-01 00:00:00
abstract::Pregnancy is a specific dynamic state, and the potential usefulness of caring for a disorder in the fetus or the mother is now well established. Previously, pregnant women have been excluded from clinical trials, therefore only a few studies concerning evaluation of the pregestational metabolism or transplacental tran...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528020-00006
更新日期:1995-02-01 00:00:00
abstract::The safety profile of any pharmacological agent is defined on the basis of its toxicity, tolerability and potential for pharmacokinetic and/or pharmacodynamic interactions with other compounds, which may belong to the same or to a different pharmacological class. Drug-drug interactions are important in clinical practi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835020-00003
更新日期:1998-08-01 00:00:00
abstract::Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and early 1970s. Clinical pharmacokinetic monitoring (CPM) helped many pharmacists to enter the clinical arena, but the focus was more on the pharmacists and tools. With the widespread acceptance of pharmaceutical care and patient-focused pha...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199834040-00001
更新日期:1998-04-01 00:00:00
abstract::The classic approach to describe the pharmacological response to a drug is to analyse its concentration-effect relationship, using a variety of possible models such as maximum effect (Emax) models or sigmoid Emax models. The aim of this review is to discuss an alternative way of describing the pharmacological effect i...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936050-00005
更新日期:1999-05-01 00:00:00
abstract::Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199222020-00004
更新日期:1992-02-01 00:00:00
abstract::This article reviews the information available to assist pharmacokineticists in the prediction of metabolic drug interactions. Significant advances in this area have been made in the last decade, permitting the identification in early drug development of dominant cytochrome P450 (CYP) isoform(s) metabolising a particu...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199732030-00004
更新日期:1997-03-01 00:00:00
abstract:OBJECTIVE:To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN:Retrospective modelling study. PATIENTS AND PARTICIPANTS:18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9....
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200140010-00005
更新日期:2001-01-01 00:00:00
abstract::The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered throug...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199200221-00008
更新日期:1992-01-01 00:00:00
abstract::A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioava...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00879-x
更新日期:2020-08-01 00:00:00
abstract::In the past decade, fludarabine has had a major impact in increasing the effectiveness of treatment of patients with indolent B-cell malignancies. This has come about in a variety of clinical circumstances, including use of fludarabine alone as well as in combinations with DNA-damaging agents or membrane-targeted anti...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241020-00002
更新日期:2002-01-01 00:00:00
abstract::Nintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-de...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-019-00766-0
更新日期:2019-09-01 00:00:00
abstract::The pharmacokinetic effect of extracorporeal elimination can be evaluated from the extracorporeal elimination rate constant, from the amount of drug removed, and from extracorporeal clearance. To compare the validity of these approaches in clinical practice, the effect of multiple plasma exchanges on the steady-state ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198510060-00004
更新日期:1985-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokineti...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-015-0347-2
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Bayesian forecasting (BF) methods for tobramycin dose individualisation has not seen widespread clinical adoption, despite being endorsed by clinical practice guidelines. Several freeware and commercial programmes using BF methods are available to support personalised dosing. This study evalua...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0610-9
更新日期:2018-08-01 00:00:00
abstract::Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthyl-alkanone class. Nabumetone is metabolised to an active metabolite 6-methoxy-2-napthylacetic acid (6-MNA) which is a relatively selective cyclo-oxygenase-2 inhibitor that has anti-inflammatory and analgesic properties. Nabumet...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199733060-00001
更新日期:1997-12-01 00:00:00
abstract::Sex-related differences in the disposition of some analgesics, anxiolytics and hypnotics have recently been reported. With certain benzodiazepines, sex has been shown to be a more important determinant of variability in drug disposition than age, while with other benzodiazepines an age-related decline in clearance was...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409030-00001
更新日期:1984-05-01 00:00:00
abstract::Many antiarrhythmic drugs introduced into the market during the past three decades have a chiral centre in their structure and are marketed as racemates. Most of these agents, including disopyramide, encainide, flecainide, mexiletine, propafenone and tocainide, belong to class I antiarrhythmics, whereas verapamil is a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241080-00001
更新日期:2002-01-01 00:00:00
abstract::The present article should be read in conjunction with the original review published in the Journal in 1983. There is no new information of major significance about the pharmacokinetics of levonorgestrel, norethisterone (norethindrone) or ethinylestradiol, although it has been shown that the concentrations of these ho...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199120010-00002
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:Zanamivir, a clinically proven potent and specific inhibitor of influenza A and B neuraminidase, has been approved in some countries for the treatment of influenza and is in late-stage development for the prophylaxis of influenza. This study investigated whether the coadministration of zanamivir and influenza...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199936001-00006
更新日期:1999-01-01 00:00:00
abstract::The ability of a wide variety of anionic, cationic, and neutral drugs to bind in a reversible manner to plasma proteins has long been recognised. Non-steroidal anti-inflammatory drugs (NSAIDs) are distinguished as a class by the high degree to which they bind to plasma protein. Plasma protein binding properties are pr...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198712060-00002
更新日期:1987-06-01 00:00:00
abstract::According to recent clinical consensus, pharmacotherapy of inflammatory bowel disease (IBD) is, or should be, personalized medicine. IBD treatment is complex, with highly different treatment classes and relatively few data on treatment strategy. Although thorough evidence-based international IBD guidelines currently e...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-018-0639-4
更新日期:2018-09-01 00:00:00
abstract::Cancer chemotherapy doses are empirical in that the majority are administered at a fixed dose (mg/m2 or mg/kg). One reason for this is the intrinsic sensitivity of the tumour or host cells to one particular chemotherapy agent is unknown. Therefore, the likelihood of response or toxicity is unpredictable a priori. This...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199732040-00005
更新日期:1997-04-01 00:00:00