Abstract:
:Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal tract and its systemic bioavailability (about 55%) is reduced because of first-pass metabolism. It undergoes rapid biodegradation to produce the microbiologically active 14-hydroxy-(R)-metabolite. The maximum serum concentrations of clarithromycin and its 14-hydroxy metabolite, following single oral doses, are dose proportional and appear within 3 hours. With multiple doses, steady-state concentrations are attained after 5 doses and the maximal serum concentrations of clarithromycin and of the 14-hydroxy derivative appear within 2 hours after the last dose. Clarithromycin is well distributed throughout the body and achieves higher concentrations in tissues than in the blood. Also, the 14-hydroxy metabolite exhibits high tissue concentrations, with values about one-third of the parent compound concentrations. The presence of food appears to have no clinically significant effect on clarithromycin pharmacokinetics. The main metabolic pathways are oxidative N-demethylation and hydroxylation, which are saturable and result in nonlinear pharmacokinetics. The primary metabolite (14-hydroxy derivative) is mainly excreted in the urine with the parent compound. A reduction in urinary clearance in the elderly and in patients with renal impairment is associated with an increase in area under the plasma concentration-time curve, peak plasma concentrations and elimination half-life. Mild hepatic impairment does not significantly modify clarithromycin pharmacokinetics. In conclusion, clarithromycin, because of its antibacterial activity and pharmacokinetic properties, appears to be a useful alternative to other macrolides in the treatment of community acquired infections.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Fraschini F,Scaglione F,Demartini Gdoi
10.2165/00003088-199325030-00003subject
Has Abstractpub_date
1993-09-01 00:00:00pages
189-204issue
3eissn
0312-5963issn
1179-1926journal_volume
25pub_type
杂志文章,评审abstract::Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness. Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibact...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241100-00004
更新日期:2002-01-01 00:00:00
abstract::First-pass elimination takes place when a drug is metabolised between its site of administration and the site of sampling for measurement of drug concentration. Clinically, first-pass metabolism is important when the fraction of the dose administered that escapes metabolism is small and variable. The liver is usually ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409010-00001
更新日期:1984-01-01 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::The alignment of drug metabolism and pharmacokinetic departments with drug discovery has not produced a radical improvement in the pharmacokinetic properties of new chemical entities. The reason for this is complex, reflecting in part the difficulty of combining potency, selectivity, water solubility, metabolic stabil...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241130-00001
更新日期:2002-01-01 00:00:00
abstract::Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. T...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-015-0351-6
更新日期:2016-06-01 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::Fluvoxamine is a selective inhibitor of serotonin reuptake that is widely used in the management of depression. Following oral administration, the drug is absorbed efficiently from the gastrointestinal tract. Peak plasma concentrations are usually observed within 2 to 8 hours postdose for capsules and film-coated tabl...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199427030-00002
更新日期:1994-09-01 00:00:00
abstract::Fluconazole was recently developed for the treatment of superficial and systemic fungal infections. Triazole groups and insertion of 2 fluoride atoms increase the polarity and hydrosolubility of the drug, allowing it to be used in a parenteral form. Bioassay methods using Candida pseudotropicalis as a test organism we...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199324010-00002
更新日期:1993-01-01 00:00:00
abstract::Ertugliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), is approved in the US, EU, and other regions for the treatment of adults with type 2 diabetes mellitus (T2DM). This review summarizes the ertugliflozin pharmacokinetic (PK) and pharmacodynamic data obtained during phase I clinical developm...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00875-1
更新日期:2020-08-01 00:00:00
abstract::Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528040-00005
更新日期:1995-04-01 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::For propofol clearance, allometric scaling has been applied successfully for extrapolations between species (rats and humans) and within the human bodyweight range (children and adults). In this analysis, the human bodyweight range is explored to determine for which range an allometric model with a fixed or estimated ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11319350-000000000-00000
更新日期:2010-04-01 00:00:00
abstract::Buspirone is an anxiolytic drug given at a dosage of 15 mg/day. The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936040-00003
更新日期:1999-04-01 00:00:00
abstract::Dorzolamide is a carbonic anhydrase inhibitor for topical ophthalmic application. It is used in the treatment of glaucoma to lower the intraocular pressure. After absorption via the cornea and stroma, it inhibits carbonic anhydrase in the ciliary process, which leads to a reduction of aqueous humour production and the...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241030-00004
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Buprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00939-2
更新日期:2020-09-17 00:00:00
abstract:OBJECTIVE:The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percu...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-015-0320-0
更新日期:2016-03-01 00:00:00
abstract::Inpatients (n = 57) on long term prophylaxis with 2 oral phenytoin preparations were followed up via monthly checks of serum drug concentrations. Duplicate serum aliquots were submitted to 2 laboratories, and covariance analysis was used to estimate laboratory error. The laboratory-associated variance of examinations ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199120040-00007
更新日期:1991-04-01 00:00:00
abstract::Drug-drug, drug-formulation and drug-meal interactions are of clinical concern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactions which may influence the gastrointestinal (GI) absorption of orally administered drugs. Abso...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936030-00004
更新日期:1999-03-01 00:00:00
abstract::A reduction in plasma albumin concentration, as seen in patients with the nephrotic syndrome, is usually associated with a decrease in plasma protein binding of highly bound drugs. Therefore, the fraction of the unbound drug increases, but the absolute free concentration remains essentially unchanged due to a compensa...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197601010-00003
更新日期:1976-01-01 00:00:00
abstract:OBJECTIVE:To evaluate the effect of cilostazol administration on warfarin pharmacokinetics and pharmacodynamics following a single 25 mg dose of warfarin. DESIGN:A randomised double-blind 2-period crossover with healthy volunteers receiving either 100 mg cilostazol twice daily for 13 days or matching placebo twice dai...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199937002-00009
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Numerous population pharmacokinetic (PK) models of tacrolimus in adult transplant recipients have been published to characterize tacrolimus PK and facilitate dose individualization. This study aimed to (1) investigate clinical determinants influencing tacrolimus PK, and (2) identify areas requ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00922-x
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:The aims of this study were to (1) determine whether opportunistically collected data can be used to develop physiologically based pharmacokinetic (PBPK) models in pediatric patients; and (2) characterize age-related maturational changes in drug disposition for the renally eliminated and hepatically metaboliz...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-018-00733-1
更新日期:2019-07-01 00:00:00
abstract::Models of tolerance are commonly derived on empirical grounds, because of lack of knowledge about the mechanism of tolerance or because of the difficulty of appropriately simplifying complex physiological processes. The present study was performed to evaluate the interchangeability of tolerance models used in the lite...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936020-00005
更新日期:1999-02-01 00:00:00
abstract::Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426060-00005
更新日期:1994-06-01 00:00:00
abstract::The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(are...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207030-00005
更新日期:1982-05-01 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::Therapeutic drug monitoring is now widely used in many areas of medicine. With its proliferation has come an understanding of the clinical situations in which it is likely to be of value. Factors that can limit the usefulness of therapeutic drug monitoring and situations where it is less likely to be of benefit have a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198713040-00001
更新日期:1987-10-01 00:00:00
abstract::25 patients with different degrees of chronic stable renal failure received oral treatment with cimetidine over 6 days and a final dose in the morning of day 7. The doses of cimetidine were reduced according to the degree of renal failure. Plasma concentrations of cimetidine were determined before the morning dose on ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198106040-00006
更新日期:1981-07-01 00:00:00
abstract::Voriconazole is both a substrate and a potent inhibitor of cytochrome P450 (CYP) 3A. It has a high bioavailability and non-linear pharmacokinetics. We investigated the pharmacokinetics and metabolism of 50 mg and 400 mg doses of intravenous and oral voriconazole in 14 healthy volunteers. Concurrently, we determined sy...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/s40262-016-0416-1
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis. METHODS:This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subj...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-019-00743-7
更新日期:2019-08-01 00:00:00