Abstract:
:Histamine H2-receptor antagonists are a unique class of compounds. Pharmacologically they are characterised as a family by their ability to inhibit the secretion of gastric acid, and kinetically they are classified as a family by their similarity in absorption, distribution and elimination. All the H2-receptor antagonists exhibit classical competitive drug-receptor interactions, with Schild slope parameters not significantly different from unity. Comparison of the values of the negative logarithm of the molar concentration of antagonist in the presence of which the potency of the agonist is reduced 2-fold (PA2) indicates that famotidine is about 20 to 50 times more potent than cimetidine and 6 to 10 times more potent than ranitidine. To date, famotidine is the most potent among marketed H2-receptor antagonists. Oral absorption of all the H2-receptor antagonists under clinical investigation is fairly rapid. Peak plasma concentrations are usually attained within 1 to 3h after the dose, but a second peak after oral administration has been observed with cimetidine, ranitidine, famotidine, ramixotidine and etintidine. The mean oral bioavailability for the H2-antagonists ranges from 50 to 70%. Reports on the plasma profiles after intravenous administration are available only for cimetidine, ranitidine, famotidine and nizatidine: plasma concentrations of all 4 decline in a biexponential manner. All of the H2-antagonists are eliminated quite rapidly, with a terminal half-life of 1 to 3h and a total body clearance of 24 to 48 L/h. Elimination is mainly attributable to renal excretion, with renal clearances ranging from 13.8 to 30 L/h. As the values for renal clearance greatly exceed the glomerular filtration rate (6 to 7.2 L/h), it is apparent that renal tubular secretion plays an important role. There is a simple, direct correlation between plasma concentrations of H2-receptor antagonists and the inhibition of gastric acid secretion. This implies a rapid equilibration between drug concentration in plasma and at the site of action, and a reversible drug-receptor interaction. Success in correlating the plasma concentration of H2-receptor antagonists and their pharmacological effects stems from reliable and precise measurement of both items. Despite the heterogeneous nature of data sources, 50% inhibitory concentration (IC50) values for cimetidine, ranitidine, famotidine, nizatidine, etintidine and roxatidine obtained in vitro appear to be in good agreement with those determined in vivo. These results suggest that at an early stage of development of an H2-receptor antagonist, IC50 determined from in vitro studies may be useful as a first approximation to predict the clinically effective concentration of the new agent.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Lin JHdoi
10.2165/00003088-199120030-00004subject
Has Abstractpub_date
1991-03-01 00:00:00pages
218-36issue
3eissn
0312-5963issn
1179-1926journal_volume
20pub_type
杂志文章,评审abstract::The influence of anaesthesia and surgery on the pharmacokinetics of pethidine (meperidine) was studied in 12 patients. Plasma pethidine concentrations in central venous blood collected during anaesthesia and the ensuing postoperative hours were by gas chromatography with electron capture detection. Postoperative analg...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207020-00004
更新日期:1982-03-01 00:00:00
abstract:: ...
journal_title:Clinical pharmacokinetics
pub_type: 评论,信件
doi:10.1007/s40262-018-0665-2
更新日期:2018-07-01 00:00:00
abstract::Since up to 90% of a theophylline dose is biotransformed, drugs influencing microsomal enzyme systems in the liver may affect the elimination of theophylline. Other integrated mechanisms (e.g. hepatic uptake) may also be altered by concurrent administration of other drugs. Whatever the mechanism, the interaction may b...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409040-00002
更新日期:1984-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Two phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS:A parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhib...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0283-1
更新日期:2015-10-01 00:00:00
abstract::The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199120060-00003
更新日期:1991-06-01 00:00:00
abstract:OBJECTIVE:To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. DESIGN:Nonblind, randomised, 2-way crossover trial. PARTICIPANTS:19 healthy volunteers (7 females, 12 males), me...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140030-00006
更新日期:2001-01-01 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::Necitumumab is a second-generation, recombinant, human immunoglobulin G1, epidermal growth factor (EGFR) receptor antibody that specifically blocks the ligand binding site of EGFR. Necitumumab potentially acts by blocking ligand epidermal growth factor (EGF) binding-mediated activation of the EGFR signaling pathway, i...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0452-x
更新日期:2017-05-01 00:00:00
abstract::The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined dur...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s40262-016-0431-2
更新日期:2017-02-01 00:00:00
abstract::Fluorouracil is used clinically against various solid tumours. Both fluorouracil toxicity and pharmacokinetics vary highly within and between individuals. The reasons why doses are not individualised routinely are difficulties in defining, predicting and achieving an optimal fluorouracil exposure or dose because of a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645060-00002
更新日期:2006-01-01 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::Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its rol...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200342060-00005
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:A prospective pharmacokinetic study was performed in Caucasian patients from an intensive care unit with respiratory support to evaluate the influence of this circumstance on the pharmacokinetic behaviour of levofloxacin. PATIENTS AND METHODS:A standard dosage regimen of 500 mg/day was administered to nine C...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200544060-00004
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:To assess the dose proportionality of lacidipine after single and repeated oral doses, and to obtain new information on the pharmacokinetics of the compound since improvement of the plasma assay method. DESIGN:Open, randomised, four-way cross-over trial. PARTICIPANTS:24 healthy male and female volunteers, a...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200342010-00004
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Proprotein convertase subtilisin/kexin type 9 inhibition with monoclonal antibodies such as alirocumab significantly reduces low-density lipoprotein-cholesterol levels ± other lipid-lowering therapies. We aimed to develop and qualify a population pharmacokinetics (PopPK) model for alirocumab in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,meta分析
doi:10.1007/s40262-016-0505-1
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND:Recombinant methionyl human leptin (r-metHuLeptin) has demonstrated efficacy in improving hormonal and metabolic parameters in leptin-deficient states, and it has been suggested that leptin replacement may reverse metabolic adaptations during weight loss interventions. The pharmacokinetics of subcutaneously ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200847110-00006
更新日期:2008-01-01 00:00:00
abstract::Cyclosporin is a powerful immunosuppressive drug used in transplantation medicine and to treat autoimmune diseases. It is a lipophilic molecule, with its bioavailability dependent on food, bile and other interacting factors. Cyclosporin is extensively metabolised in the liver by the cytochrome P450 3A system, which is...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199324060-00004
更新日期:1993-06-01 00:00:00
abstract::The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical im...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0572-y
更新日期:2018-02-01 00:00:00
abstract::Since its discovery in 1970, and introduction into clinical practice in 1978, cyclosporin has become the most important immunosuppressive drug used to prevent organ transplant rejection. This has been achieved by virtue of the improved graft survival rates and adverse effect profiles in patients when compared with tha...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199732050-00002
更新日期:1997-05-01 00:00:00
abstract::Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly. Additionally, antipyrine kinetics in 5 women who had previously used the injectable contraceptive for 8 to...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198611020-00007
更新日期:1986-03-01 00:00:00
abstract::Haloperidol has been used extensively for the treatment of psychotic disorders, and it has been suggested that the monitoring of plasma haloperidol concentration is clinically useful. Different assay methodologies have been used in research and clinical practice to examine the relationship between response and plasma ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198917060-00004
更新日期:1989-12-01 00:00:00
abstract:BACKGROUND:Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE....
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-016-0486-0
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Labetalol is frequently prescribed for the treatment of hypertension during pregnancy; however, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-013-0123-0
更新日期:2014-04-01 00:00:00
abstract::The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral admin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198510020-00004
更新日期:1985-03-01 00:00:00
abstract::With the use of combination chemotherapy as well as a wide range of symptomatic therapies (e.g. analgesics and antiemetics) for the treatment of patients with cancer, the field of oncology practises polypharmacy to an extreme degree. The risk for a drug interaction under these conditions is high, and the pharmacologic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198611030-00004
更新日期:1986-05-01 00:00:00
abstract::The US Food and Drug Administration (FDA) draft guidance for industry on drug interaction studies recommends, but does not mandate, that both cigarette smokers and non-smokers can be used to study drug metabolism in clinical trials, and that important results related to smoking should be included in drug labelling to ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-015-0246-6
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Because of the vulnerability and frailty of elderly adults, clinical drug development has traditionally been biased towards young and middle-aged adults. Recent efforts have begun to incorporate data from paediatric investigations. Nevertheless, the elderly often remain underrepresented in clinical trials, e...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0422-3
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Vicriviroc is a small-molecule CCR5 antagonist currently in development for the treatment of HIV in patients on a regimen containing a ritonavir-boosted protease inhibitor. As renal disease and renal dysfunction are prevalent in the HIV-infected population, patients with varying degrees of rena...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2165/11319470-000000000-00000
更新日期:2010-06-01 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::Pancuronium is frequently used in coronary artery surgery, but its pharmacokinetics in these patients are still unknown. It is possible that dopamine, administered to prevent renal impairment induced by the surgery, might promote the elimination of pancuronium. Therefore, the pharmacokinetics of a bolus dose of pancur...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199019060-00005
更新日期:1990-12-01 00:00:00