Abstract:
:The enantioselectivity of hydroxylation of nortriptyline (NT) to E-10-hydroxynortriptyline (E-10-OH-NT) was studied in human liver microsomes, intestinal homogenate, and patients treated with NT. The rate of formation of (-)-E-10-OH-NT was higher than that of (+)-E-10-OH-NT both in the liver microsomes and in the intestinal homogenate. Quinidine, a prototype competitive inhibitor of the cytochrome P450IID6 ("debrisoquin hydroxylase"), inhibited the formation of (-)-E-10-OH-NT in a concentration-dependent manner in liver microsomes, while the formation of (+)-E-10-OH-NT was hardly affected. This indicates that P450IID6 catalyzes the hydroxylation of NT in a highly enantioselective manner to (-)-E-10-OH-NT in the liver. Another P450 isozyme besides IID6 seems to be responsible for the formation of the (+)-enantiomer in the liver. In intestinal homogenate, the formation of both enantiomers of E-10-OH-NT was inhibited to about the same extent by quinidine, the maximum inhibition being much less than in the liver. In the urine of six patients treated with NT, the (-)-enantiomer accounted for 91 +/- 2% of the unconjugated E-10-OH-NT, and for 78 +/- 6% of the glucuronide conjugates. The study shows that NT is hydroxylated in a highly enantioselective way, probably catalyzed by the polymorphic P450IID6, to (-)-E-10-OH-NT both in vitro in human liver as well as in vivo in patients treated with the drug.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Dahl ML,Nordin C,Bertilsson Ldoi
10.1097/00007691-199105000-00001subject
Has Abstractpub_date
1991-05-01 00:00:00pages
189-94issue
3eissn
0163-4356issn
1536-3694journal_volume
13pub_type
杂志文章abstract::The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198303000-00004
更新日期:1983-01-01 00:00:00
abstract::Digitalis-like immunoreactive substances (DLIS) obtained from maternal and umbilical cord plasma at delivery were measured by fluorescence polarization immunoassay (FPIA; TDX, Abbott) and microparticle enzyme immunoassay (MEIA; IMX, Abbott). In each sample, concentrations of dehydroepiandrosterone, dehydroepiandroster...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200304000-00015
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:Desmopressin (D-amino D-arginine vasopressin: dDAVP) is used for the treatment of patients with hemophilia A and Von Willebrand disease. Studies on the rationale of dosing are scarce and mainly focus on the underlying causes of the vast differences in desmopressin response among individuals. The aim of this ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000791
更新日期:2020-12-01 00:00:00
abstract::Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these pati...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200006000-00004
更新日期:2000-06-01 00:00:00
abstract::Differences in product formulations have been shown to affect the therapeutic response by altering the relative bioavailability and pharmacokinetics of a drug. The relative bioavailability and pharmacokinetics of carbamazepine tablets (CBZ) and a chewable tablet formulation were evaluated in 10 normal healthy subjects...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-198703000-00006
更新日期:1987-01-01 00:00:00
abstract::Measurement of whole blood and plasma levels of cyclosporin A (CsA) by radioimmunoassay in kidney transplant recipients receiving the drug showed that CsA concentrations in plasma increased nonlinearly when whole blood levels of the drug exceeded 1,000 ng/ml. At low plasma levels (less than 200 ng/ml), most of the CsA...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198503000-00010
更新日期:1985-01-01 00:00:00
abstract::The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual pat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000701
更新日期:2020-02-01 00:00:00
abstract::When first approved, the dosing regimens for zidovudine were 1,200-1,500 mg/day; however, because toxicity developed, the daily dose had to be reduced to 500-600 mg/day. At these lower doses, plasma concentrations for a considerable segment of the dosing interval are often below the assay sensitivity for the high-perf...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199704000-00014
更新日期:1997-04-01 00:00:00
abstract::The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198309000-00014
更新日期:1983-01-01 00:00:00
abstract::An original, sensitive, and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of morphine and its two major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in human plasma and cerebrospinal fluid (CSF) and in rat plasma, using hydromorphone as ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199404000-00016
更新日期:1994-04-01 00:00:00
abstract::The aim of the current study was to compare the pharmacokinetics of phenobarbital (PB) in extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin. Ten healthy volunteers (5 EMs and 5 PMs) were given 30 mg PB daily for 14 days. PB and p-hydroxyphenobarbital (p-OHPB) in serum and urine were measured by...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200104000-00004
更新日期:2001-04-01 00:00:00
abstract::The placental and milk transfer of chloroquine was studied in seven subjects and six subjects, respectively. Seven pregnant women at term were administered chloroquine phosphate (5 mg/kg) i.m. The maternal blood and arterial and venous umbilical cord blood were obtained during delivery. The maternal chloroquine blood ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198802000-00004
更新日期:1988-01-01 00:00:00
abstract::The role of drug assays for screening, diagnosis, and guiding treatment decisions in overdose patients remains unclear. The use of drug concentration data in clinical toxicology research is more problematic, with studies using drug concentrations to simply confirm ingestion in observational studies or others report dr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181dca280
更新日期:2010-06-01 00:00:00
abstract::Theophylline clearance was estimated by a single-sample technique in 19 subjects with acute clinical respiratory infections. Mean (+/- SD) theophylline clearance during acute illness was 0.044 +/- 0.011 L X h-1 X kg-1 compared to 0.043 +/- 0.012 L X h-1 X kg-1 1 month later. In a subset of five subjects, single-sample...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198709000-00005
更新日期:1987-09-01 00:00:00
abstract:BACKGROUND:Dolutegravir (DTG) is an integrase strand transfer inhibitor, which is a newly approved antiretroviral drug used for the treatment of HIV-infected naive and experienced individuals. Many aspects of DTG pharmacology remain to be studied. Our aim was to develop and fully validate a robust analytical method for...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000286
更新日期:2016-06-01 00:00:00
abstract::An analytical technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI--MS) has been developed for the simultaneous determination of five protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, and amprenavir; and three non-nucleoside reverse transcriptase inhibitors...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200108000-00010
更新日期:2001-08-01 00:00:00
abstract::The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres. The dose was based upon the attainment of recommended serum concentrations. Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), a...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications. METHODS:Steady-state trough serum concentratio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31827a1aad
更新日期:2013-02-01 00:00:00
abstract::This study examined whether salivary nicotine concentrations would provide a useful index of plasma concentrations in studies of the effects of transdermal nicotine administration. Twenty-four subject smokers abstained from smoking for 12 h prior to admission to a clinical research unit ward and for 36 h while remaini...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199310000-00012
更新日期:1993-10-01 00:00:00
abstract::5-Methoxy-N,N-dialkyltryptamines are tryptamine derivatives that possess strong hallucinogenic effects. Because of their escalating popularity and potent physiological effects, an increasing number of acute poisoning cases have been reported in various countries. For their metabolism in humans, only a few studies have...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181dcb40c
更新日期:2010-06-01 00:00:00
abstract::The pharmacokinetics of oxycodone have been determined after single-dose administration by the intravenous (4.6-7.3 mg), oral (tablets, 9.1 mg and syrup, 9.1 mg), and rectal (30 mg) routes, in 48 patients undergoing minor surgery. There were no significant differences in the mean elimination half-lives between the int...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199212000-00008
更新日期:1992-12-01 00:00:00
abstract::Their common clinical use, frequency of adverse effects, serious therapeutic indications, treatment failures, and availability of sensitive assays make corticosteroids such as prednisone and prednisolone candidates for therapeutic drug monitoring. Complicating the interpretation of plasma drug concentrations are the f...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-198004000-00011
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e318228bb2a
更新日期:2011-10-01 00:00:00
abstract::The authors refer to their experience with alternative matrices to supervise the methadone therapy of heroin abusers. For this purpose, hair, sweat, and urine samples were collected from 10 heroin addicts and from a control group and were submitted to gas chromatographic/mass spectroscopic analysis for methadone and i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31811f1bbe
更新日期:2007-08-01 00:00:00
abstract::The authors describe a rapid, useful, specific, and very sensitive high-performance liquid chromatographic assay for the determination of fluvastatin (FV) level using atorvastatin as the internal standard (IS). After a simple deproteinization of 1.0 mL of plasma with acetonitrile, the drug and IS were extracted with t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200302000-00013
更新日期:2003-02-01 00:00:00
abstract::The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200410000-00015
更新日期:2004-10-01 00:00:00
abstract::An index of desipramine (DMI) hydroxylation, calculated as the ratio between the amounts of DMI and 2-hydroxydesipramine (2-OH-DMI) excreted in urine after 25 mg orally, was determined in 16 depressed patients. The index varied almost 100-fold between the patients and correlated significantly to the steady-state plasm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198706000-00001
更新日期:1987-06-01 00:00:00
abstract::It has been suggested that lamotrigine (LTG) may enhance the toxicity of carbamazepine (CBZ) by increasing the concentration of the active metabolite carbamazepine-10,11-epoxide (CBZ-E) in adult patients. The authors investigated this hypothesis in an add-on study in 11 children and 3 adolescents, aged 6-22 years, who...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199710000-00002
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND:The efficacy of drugs for the treatment of substance-related disorders is moderate at best. Therapeutic drug monitoring (TDM) could be an instrument to improve outcomes. Because TDM for most of those drugs is not established, the authors reviewed the literature and built a rating scale to detect the potentia...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e31822fbf7c
更新日期:2011-10-01 00:00:00
abstract::The purpose of this study was to construct a population pharmacokinetic (PK) metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous, an...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200408000-00010
更新日期:2004-08-01 00:00:00