Abstract:
BACKGROUND:The anticonvulsant properties of phenytoin (PHT) were discovered in 1938. Since then, it has been one of the most widely used antiepileptic drugs. It is slowly absorbed, extensively plasma protein-bound, exhibits a nonlinear, concentration-dependent pharmacokinetic profile, and has a narrow therapeutic range. METHODS:We determined PHT bioavailability during steady-state therapy by 1) measurement of the two principal deconjugated PHT urinary metabolites, 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin (DHD); and 2) direct determination of absolute bioavailability after simultaneous administration of an oral formulation and parenteral stable-labeled PHT (SL-PHT). Urinary metabolites were quantified by an isocratic HPLC-NI-APCI-MS method. The urinary dose recovery was calculated by dividing the molar recovery of the major PHT urinary metabolites by the molar dose received. RESULTS:Urinary metabolite recovery was surprisingly low, 35.4% ± 15.7% in younger patients (age 21-49 years old) and 32.9% ± 15.0% in patients aged 65 to 93 years. Absolute bioavailability was 86.4% ± 19.4% and 92.5% ± 25.2%, respectively. A weak, but significant, Spearman rank correlation was observed between urinary metabolite recovery and oral bioavailability (P = 0.00924, R = 0.166). CONCLUSION:This weak correlation may be the result of variability in urinary versus biliary-fecal excretion of p-HPPH glucuronide. This study demonstrates that daily PHT oral absorption exhibits wide interpatient variability, which may account for fluctuations in PHT concentration over time.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Aliwarga T,Cloyd JC,Goel V,Brundage RC,Marino SE,Leppik IE,Remmel RPdoi
10.1097/FTD.0b013e3182081089subject
Has Abstractpub_date
2011-02-01 00:00:00pages
56-63issue
1eissn
0163-4356issn
1536-3694pii
00007691-201102000-00010journal_volume
33pub_type
杂志文章abstract::Australia is blessed with a great diversity of unique species in its fresh waters and in the marine environment around its coast. There is evidence that human and natural events are impacting on these species. Such impacts are associated with various agricultural, industrial, and domestic practices and with natural an...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200002000-00012
更新日期:2000-02-01 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
abstract:BACKGROUND:The association of CYP3A5, CYP3A4, and ABCB1 single nucleotide polymorphisms (SNPs) with cyclosporine (CsA) pharmacokinetics is controversial. The authors studied the influence of these SNPs on CsA pharmacokinetics as well as on the incidence of biopsy-proven acute rejection (BPAR) and renal function after k...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FTD.0b013e31820feb8e
更新日期:2011-04-01 00:00:00
abstract::Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were g...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819566f1
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Nivolumab is a fully humanized IgG4 monoclonal antibody that targets the programmed death-1 (PD-1) receptor, disrupting PD-1-mediated signaling and restoring antitumor immunity. The objective of this study was to develop a nivolumab quantification method using liquid chromatography-tandem mass spectrometry (...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000558
更新日期:2018-12-01 00:00:00
abstract::A highly sensitive, specific method for determining chloramphenicol levels in human blood plasma and cerebrospinal fluid is described. The method uses high performance liquid chromatography for the analysis, requires minimal quantities of patient specimen, and thus is suitable for use in newborn and pediatric patients...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198709000-00016
更新日期:1987-09-01 00:00:00
abstract::A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200012000-00011
更新日期:2000-12-01 00:00:00
abstract::The TDx digoxin II immunoassay was used in controls and in patients not taking digoxin or any other cardiac glycoside. We report the frequency of interference thought to be caused by digoxin-like factors (DLFs). We found a high incidence of false-positive results in 15 patients with severe hepatic disease (60% false-p...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199111000-00010
更新日期:1991-11-01 00:00:00
abstract::A rapid and reliable micro procedure for the high pressure liquid chromatographic analysis of cimetidine. N"-cyano-N-methyl-N'-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]guanidine, in serum or plasma is described. The percentage analytical recovery of cimetidine and internal standard (beta-hydroxypropyl-theophy...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-197901030-00010
更新日期:1979-01-01 00:00:00
abstract::Specific chromatographic methods for the measurement of cyclosporin A, tacrolimus, sirolimus, and everolimus blood levels in patients with organ transplants are time consuming when large numbers of samples must be processed. The authors developed a robust and fast (1 minute) online solid-phase extraction liquid chroma...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181c49a00
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Quality management and accreditation in the analytical laboratory setting are developing rapidly and becoming the standard worldwide. Quality management refers to all the activities used by organizations to ensure product or service consistency. Accreditation is a formal recognition by an authoritative regul...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31828526b4
更新日期:2013-06-01 00:00:00
abstract::Plasma clonazepam (CZP) and its metabolite [7-aminoclonazepam (7ACZP) and 7-acetamidoclonazepam (7AACZP)] concentrations were measured during a single dosing interval in 10 pediatric epilepsy patients (2-18 years, 11-102 kg) who had been receiving CZP therapeutically from 2 weeks to 4 years. These concentrations were ...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199602000-00001
更新日期:1996-02-01 00:00:00
abstract::There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples take...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/01.ftd.0000167885.17280.6f
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic reg...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000261
更新日期:2016-04-01 00:00:00
abstract::A high-performance liquid chromatographic method for the determination of linezolid in human plasma was developed and validated. After precipitation of plasma proteins with perchloric acid, the protein-free supernatant was separated by isocratic reverse-phase chromatography on a X Bridge C18 column. The mobile phase c...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181d5eeee
更新日期:2010-08-01 00:00:00
abstract::The analysis of pemoline (2-imino-5-phenyl-4-oxazolidine) by a rapid, sensitive, and specific high performance liquid chromatographic assay using ultraviolet detection is described. Only 100 microliters of plasma or serum is required. Analytical recoveries of 88% for pemoline and 93% for the internal standard (4-methy...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198007000-00009
更新日期:1980-01-01 00:00:00
abstract::Hydroxylation of midazolam (MDZ) is mediated almost exclusively by CYP3A isoforms. The authors describe a high-performance liquid chromatography assay involving MDZ, 1'-hydroxymidazolam, and 4-hydroxymidazolam in plasma. The compounds were eluted on an Ultrasphere ODS, 3-microm particle size, 7.5 cm x 4.6 mm reversed-...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199806000-00013
更新日期:1998-06-01 00:00:00
abstract::Four different immunoassays were used to measure cyclosporine A (CsA) plasma (20 degrees C) levels in heart and kidney transplant recipients. Two radioimmunoassays (RIAs) (Sandimmune and Cyclotrac) and the fluorescence polarization immunoassay (FPIA) were based on polyclonal antibodies, whereas the fourth (Cyclotrac-S...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199011000-00006
更新日期:1990-11-01 00:00:00
abstract::The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or th...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198911000-00013
更新日期:1989-11-01 00:00:00
abstract::Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum prote...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199202000-00009
更新日期:1992-02-01 00:00:00
abstract::In a phase I-II study, the authors evaluated the intracellular pharmacokinetics, toxicity, and efficiency of a high dose of mitoxantrone given as first induction in acute non-lymphocytic leukemia. Twenty-two patients with previously untreated de novo ANLL were included and received 30 or 40 mg/m2 mitoxantrone on day 1...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199812000-00010
更新日期:1998-12-01 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::The effect of ofloxacin taken for 8 days (200 mg twice daily) on the pharmacokinetics of a single intravenous dose of theophylline (4.3 mg/kg over 15 min) was studied in a crossover procedure among seven healthy male volunteers. Theophylline concentrations were measured serially for 10 h by the immunofluorescence pola...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198802000-00007
更新日期:1988-01-01 00:00:00
abstract::A 64-year-old man on chronic hemodialysis for end-stage renal disease developed peritoneal carcinomatosis, and palliative chemotherapy with fluorouracil was started. The drug was administered (325 mg/m as IV bolus, at 2 PM) on 2 separate occasions, ie, 1 hour after dialysis and 2 days later, 49 hours after dialysis. T...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000183384.89275.f4
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Paclitaxel (PTX; Taxol, Abraxane) is used in many regimens for breast cancer, non-small cell lung cancer (NSCLC), and ovarian cancer. Multiple studies have demonstrated that PTX exhibits a greater than 10-fold interpatient variability of clearance rates when patients are dosed according to body surface area ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e318296be01
更新日期:2013-12-01 00:00:00
abstract::A simple and rapid reversed-phase C-18 high-performance liquid chromatography (HPLC) assay without a prior extraction step for dihydroquinidine (HQD) in serum is described. The method is selective and useful for monitoring HQD and its presumed metabolites, quinidine (QD), N-oxide QD, 3-hydroxy QD (3-OHQD), and 10-11-d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198412000-00017
更新日期:1984-01-01 00:00:00
abstract::The analysis of pentamidine in whole blood, plasma, and urine by liquid chromatography is described. Extraction was made with a mixture of acetonitrile and chloroform followed by back-extraction into phosphate buffer. A reversed-phase chromatographic system with fluorescence detection was used. The precision of the me...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199007000-00011
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND:Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000429
更新日期:2017-10-01 00:00:00
abstract::The immunosuppressant mycophenolic acid (MPA) used for solid organ transplantation is predominantly metabolized to a pharmacologically inactive phenolic glucuronide (MPAG) and, to a lesser extent, to the pharmacologically active acyl glucuronide (AcMPAG). The recently introduced CEDIA Mycophenolic Acid Assay from Micr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181cc342a
更新日期:2010-02-01 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