Abstract:
BACKGROUND:Fosphenytoin, the diphosphate ester salt of phenytoin, is widely used to treat status epilepticus. The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patients. METHODS:Patient backgrounds, laboratory tests, and prescribed drugs were retrospectively collected from electronic medical records. Patients who received fosphenytoin were enrolled. The PPK analysis was performed using NONMEM 7.3.0 with the first-order conditional estimation method with interaction. Age, sex, laboratory tests, and coadministered drugs were selected as candidates for covariates. Significance levels for forward inclusion and backward elimination were set at 0.05 and 0.01, respectively. The study protocol was approved by the Fukuoka Tokushukai Ethics Committee. RESULTS:A total of 340 serum phenytoin concentrations from 200 patients treated with fosphenytoin were available. The median age and body weight of the population were 71 years and 53.4 kg, respectively. A linear 1-compartment model with the conversion rate of fosphenytoin to phenytoin clearly described the pharmacokinetics of phenytoin after the intravenous administration of fosphenytoin. Age was detected as a covariate of clearance (CL): CL (L/h) = 1.99 × (body weight/53.4) × (age/71). Goodness-of-fit plots revealed the high-predictive performance of the final PPK model, and systematic deviations were not observed. The final model was validated by a prediction-corrected visual predictive check and bootstrap analysis. CONCLUSIONS:We herein developed a PPK model to describe phenytoin concentrations after the intravenous administration of fosphenytoin. Age was identified as a significant covariate for CL.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Higuchi K,Yamashita D,Kashihara Y,Kakara M,Hirota T,Hirakawa M,Ieiri Idoi
10.1097/FTD.0000000000000651subject
Has Abstractpub_date
2019-10-01 00:00:00pages
674-680issue
5eissn
0163-4356issn
1536-3694journal_volume
41pub_type
杂志文章abstract::Mixed-effect modeling has been suggested as a possible tool to detect and describe drug interactions in patient populations receiving drug combinations for the treatment of disease states. The mixed-effect modeling program, NONMEM, was used to measure the effects of the well-known digoxin-quinidine and digoxin-verapam...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199602000-00008
更新日期:1996-02-01 00:00:00
abstract::Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lea...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/01.ftd.0000211834.41844.82
更新日期:2006-06-01 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:BACKGROUND:Antiepileptic drug therapeutic regimens often need to be adjusted individually on the basis of serum assays. We aimed to develop a quantitative, fast, and sensitive liquid chromatography-tandem mass spectrometry method to simultaneously analyze carbamazepine, oxcarbazepine, and the 10-11 epoxide carbamazepin...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3182425168
更新日期:2012-02-01 00:00:00
abstract::Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200306000-00002
更新日期:2003-06-01 00:00:00
abstract::Individualized tobramycin therapy was systemically evaluated in 26 patients with gram-negative pneumonias involving Pseudomonas aeruginosa and other multiple antibiotic-resistant pathogens. Patient prognoses were classified by underlying diseases, and response was determined according to previously established criteri...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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更新日期:1980-01-01 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
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doi:10.1097/FTD.0b013e31828526b4
更新日期:2013-06-01 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::A sensitive method is described for the simultaneous determination of mebendazole and hydroxymebendazole using flubendazole as an internal standard. The analytes were isolated with a single chloroform extraction from 1.0 ml of alkalinized plasma or cyst liquid samples. Separation and quantitation were performed with h...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198406000-00015
更新日期:1984-01-01 00:00:00
abstract::A rapid and simultaneous determination of several analgesic antiinflammatory agents--ibuprofen, acetaminophen, indomethacin, and salicylic acid--in human serum was developed by using capillary zone electrophoresis (CZE) coupled with diode-array ultraviolet detection. After precipitation of serum protein with acetonitr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:In humans, donepezil (D) is metabolized to 5-O-desmethyl-donepezil (5DD), 6-O-desmethyl-donepezil (6DD), and donepezil-N-oxide (DNox). Although 6DD and DNox are pharmacologically active, the activity of 5DD is unknown. At present, no routine methods are available to detect D and its 3 metabolites simultaneou...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000246
更新日期:2016-02-01 00:00:00
abstract::Despite its known teratogenic effects, thalidomide has been used to treat a variety of diseases ranging from alleviation of autoimmune disorders to prevention of metastasis of cancers. The exact method of action of thalidomide and its derivatives is still under investigation. Thalidomide undergoes very little metaboli...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200202000-00017
更新日期:2002-02-01 00:00:00
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::The authors report the use of high-performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantification of indomethacin (IND) in plasma with microscale sample preparation. Plasma samples (100 microL) and mefanamic acid (internal standard [IS]), buffered to pH 3.5, were prepar...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199812000-00020
更新日期:1998-12-01 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::Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1988-01-01 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:BACKGROUND:Colistin is increasingly used as the last therapeutic option for the treatment of multidrug-resistant, Gram-negative bacterial infections. To ensure safe and efficacious use of colistin, therapeutic drug monitoring (TDM) is needed due to its narrow therapeutic window. This study aimed to evaluate the pharmac...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0000000000000572
更新日期:2019-02-01 00:00:00
abstract::Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrom...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200106000-00008
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::We have suggested previously that acute tolerance to the chronotropic effect of cocaine develops and that tolerance is incomplete, such that the heart-rate decline in the presence of stable plasma cocaine concentrations approaches a plateau that exceeds the baseline heart rate. One possible mechanism for heart-rate de...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199312000-00015
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3182804c9b
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:To increase target attainment rates, switching the mode of administration from intermittent (InI) to continuous infusion (CoI) has been proposed. In this study, target attainment rates and interpatient variation in exposure were compared between vancomycin InI- and CoI-treated critically ill patients. METHO...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000295
更新日期:2016-06-01 00:00:00
abstract::Phenytoin is an anticonvulsant that requires therapeutic drug monitoring. Recently, Bayer HealthCare, Diagnostics Division released a turbidimetric immunoassay of phenytoin on the ADVIA 1650 analyzer. We evaluated the analytic performance of this assay by comparing values obtained in 52 patients receiving Phenytoin us...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000164315.13825.dd
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:Therapeutic drug monitoring (TDM) involves the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50% of hypertensive patients treated with l...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000806
更新日期:2021-02-01 00:00:00
abstract:BACKGROUND:The Clinical Pharmacology Quality Assurance (CPQA) program provides semiannual proficiency testing (PT) of antiretroviral analytes for 11 US and international clinical pharmacology laboratories (CPLs) to ensure interlaboratory comparability. In this article, we provide estimates of the main sources of variab...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000612
更新日期:2019-08-01 00:00:00
abstract::A computer-based approach for estimating pharmacokinetic data and predicting plasma drug concentrations based on two measurements of plasma drug concentrations was compared with a standard two-point method for estimating aminoglycoside (AG) pharmacokinetic parameters. The computer-based technique was also used to pred...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198507030-00003
更新日期:1985-01-01 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::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:Human immunodeficiency virus (HIV)-infected individuals show large interindividual variation in response to antiretroviral therapy. Efavirenz (EFV) and nevirapine (NVP) are nonnucleoside reverse transcriptase inhibitors, which are prescribed in combination with other antiretroviral therapy in so-called highl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31824868f3
更新日期:2012-04-01 00:00:00