scholarly journals Prediction of steady-state plasma concentrations of olanzapine in Chinese Han in patients based on a retrospective population pharmacokinetic model

2021 ◽  
Vol 20 (11) ◽  
pp. 2433-2441
Author(s):  
Xiaoyue Wang ◽  
Yong Han ◽  
Hong Zhou ◽  
Bin Cao ◽  
Miaomiao Zhu ◽  
...  
Keyword(s):  
Steady State ◽  
Smoking Status ◽  
Mental Health Center ◽  
Plasma Concentrations ◽  
Visual Predictive Check ◽  
Apparent Volume ◽  
Population Pharmacokinetic ◽  
Chinese Han ◽  
Mixed Effect ◽  
State Plasma

Purpose: To develop robust methods of establishing a population pharmacokinetics (Pop-PK) model of olanzapine, using existing hospital in-patient information, in order to predict the steady-state plasma concentration of olanzapine tablets in Chinese Han inpatients, thus providing guidance for individualized therapy for mental disorders.Methods: A retrospective study analyzing and predicting the steady-state plasma olanzapineconcentration was performed using nonlinear mixed-effect modeling (Phoenix® NLME8). The effects of ten potential covariates, including age, gender, Body Mass Index, fasting lipid, family history, alcohol and smoking status in 107 Chinese Han patients with steady-state plasma olanzapine concentration were collected from the hospital information system (HIS) in Wuhan Mental Health Center from Feb 2017 to Jul 2019.Results: The final model was validated using bootstrap and visual predictive check (VPC) and was found to fit the one-compartment mixed error model. Smoking status was found to be the only factor affecting olanzapine tablets clearance. The standard Pop-PK parameters apparent volume of distribution (VL/F) and clearance (CL/F) were 223 L and 12.4 Lꞏh-1, respectively.Conclusion: The Pop-PK model for olanzapine established with the data from HIS is effective inpredicting the plasma olanzapine tablets concentration of individual Chinese in-patients. This Pop-PK model approach can now be adapted to optimize other antipsychotic drugs.

scholarly journals Fasting Remnant Lipoprotein Cholesterol and Triglyceride Concentrations Are Elevated in Nondiabetic, Insulin-Resistant, Female Volunteers1

1999 ◽  
Vol 84 (11) ◽  
pp. 3903-3906 ◽  
Author(s):  
Fahim Abbasi ◽  
Tracey McLaughlin ◽  
Cindy Lamendola ◽  
Helen Yeni-Komshian ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Insulin Resistant ◽  
Remnant Lipoprotein ◽  
Increased Risk ◽  
Resistant Group ◽  
State Plasma

This study was initiated to test the hypothesis that plasma concentrations of remnant lipoproteins would be higher after an overnight fast in insulin-resistant compared to insulin-sensitive volunteers. Forty-three healthy nonobese women were studied, divided into insulin-resistant (n = 21) and insulin-sensitive (n = 22) groups on the basis of their steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide acetate, insulin, and glucose. Under these conditions, steady state plasma insulin concentrations are similar in all subjects (∼60μ U/mL), and the higher the SSPG concentrations, the more insulin resistant the individual. By selection, mean (±sem) SSPG concentrations were significantly higher (P < 0.001) in the insulin-resistant group (210 ± 7 vs. 78 ± 3 mg/dL). In addition, the insulin-resistant group had higher triglycerides (198 ± 27 vs. 101 ± 12 mg/dL; P < 0.005) and lower high density lipoprotein cholesterol (48 ± 4 vs. 60 ± 4 mg/dL; P < 0.05) concentrations. Finally, insulin resistance was associated with higher remnant lipoprotein particle concentrations of cholesterol (7.2 ± 0.8 vs. 4.4 ± 0.3; P < 0.005) and triglycerides (22.2 ± 3.4 vs. 8.5 ± 1.0; P < 0.001). All of these differences were seen despite the fact that the two groups were similar in terms of age and body mass index. These results identify additional abnormalities in lipoprotein metabolism that may contribute to the increased risk of coronary heart disease seen in insulin-resistant, nondiabetic subjects (syndrome X).

scholarly journals Population pharmacokinetic study of teicoplanin in severely neutropenic patients.

1996 ◽  
Vol 40 (5) ◽  
pp. 1242-1247 ◽  
Author(s):  
O Lortholary ◽  
M Tod ◽  
N Rizzo ◽  
C Padoin ◽  
O Biard ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Linear Regression Analysis ◽  
Central Compartment ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
Elimination Half ◽  
Neutropenic Patients ◽  
The Mean ◽  
Volumes Of Distribution

The teicoplanin pharmacokinetics (PK) of 30 febrile and severely neutropenic patients (polymorphonuclear count, < 500/mm3) with hematologic malignancies were compared with those determined for five healthy volunteers (HV). Neutropenic patients were given piperacillin combined with amikacin, and teicoplanin was added to the regimen the day fever developed in patients suspected of having a staphylococcal infection or 48 h later. Teicoplanin was given intravenously at a dosage of 6 mg/kg of body weight at 0, 12, and 24 h and once a day thereafter. Five to eleven blood samples per patient were collected. Teicoplanin concentrations were measured by liquid chromatography. A bicompartmental model was fitted to the data by a nonlinear mixed-effect-model approach. Multiple-linear regression analysis was applied in an attempt to correlate PK parameters to nine covariates. The mean trough concentrations of teicoplanin 48 h after the onset of treatment and 24 h after the last injection (last trough) +/- standard deviations were 8.8 +/- 4.1 and 17.5 +/- 13.5 mg/liter, respectively. A significant increase was noted in the mean rate of elimination clearance of teicoplanin in neutropenic patients compared with that of HV (0.86 versus 0.73 liter/h, P = 0.002), as was the case with rates of distribution clearance (5.89 versus 4.94 liter/h, P = 0.002); the mean half-life of distribution was significantly shorter in patients than in HV (0.43 versus 0.61 h, P = 0.002). In contrast, the volumes of the central compartment (ca. 5.8 liters for both groups), the volumes of distribution at steady state (HV, 37.6 liters; patients, 55.9 liters), and the elimination half-lives (HV, 39.6 h; patients, 52.7 h) were not significantly different between HV and neutropenic patients. Interindividual variabilities of rates of clearance (coefficient of variation [CV], 43%) and elimination half-lives (CV, 56%) were mainly explained by the variabilities among rates of creatinine clearance. Interindividual variabilities of the volumes of the central compartment (CV, 33%) and the volumes of distribution at steady state (CV = 51%) were correlated to interindividual variabilities among numbers of leukocytes and the ages of patients, respectively. On the basis of the population PK model of teicoplanin, simulations were made to optimize the dosing schedule. A supplemental 6 mg/kg dose of teicoplanin at 36 h resulted in a trough concentration at 48 h of 16.0 +/- 4.5 mg/liter, with only 7% of patients having a trough concentration of less than 10 mg/liter, compared with 46% of patients on the usual schedule.

Daily Variations in Steady-State Plasma Concentrations of Carbamazepine and its Metabolites in Epileptic Children

1991 ◽  
Vol 20 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Ronald Hartley ◽  
W. Ian Forsythe ◽  
Bruce McLain ◽  
Pak C. Ng ◽  
Mark D. Lucock
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Daily Variations ◽  
Epileptic Children ◽  
State Plasma

CYP2D6 genotypes in association with steady state plasma concentrations of active metabolites of tamoxifen in patients with breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 634-634 ◽  
Author(s):  
H. Lim ◽  
H. Lee ◽  
K. Lee ◽  
E. Lee ◽  
I. Jang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Plasma Concentrations ◽  
Cancer Center ◽  
Cyp2d6 Genotype ◽  
Active Metabolites ◽  
Fluorescence Detector ◽  
Wilcoxon Rank Sum Test ◽  
Center Hospital ◽  
State Plasma

634 Background: Tamoxifen is a prodrug that is metabolized to active metabolites, Z-4-hydroxy-N-desmethyltamoxifen (BX) and Z-4-hydroxy-tamoxifen (4OH) where CYP2D6 plays a major role in the conversion. Genetic polymorphisms of CYP2D6 by ethnicities are well known with CYP2D6*10 in Asians (up to 50% in Koreans), and CYP2D6 *2 and *4 in American Whites as major variant alleles. We analyzed the steady state plasma concentrations of tamoxifen and its metabolites in patients (pts) with breast cancer to evaluate their associations with various CYP2D6 genotypes. Methods: Blood samples were collected from 219 pts on tamoxifen, 20 mg daily as adjuvant therapy for more than 3 months at National Cancer Center, Korea. Plasma tamoxifen, N-desmethyltamoxifen, BX, 4OH were measured by validated HPLC with fluorescence detector, and analyzed according to CYP2D6 genotype groups by Wilcoxon rank sum test. CYP2D6*10, CYP2D6*5 and CYP2D6*2×2 were identified by PCR-RFLP methods, and the rests were classified as CYP2D6*1 (wild type). This study was approved by IRB at National Cancer Center Hospital (NCCNHS04–033) and conducted after informed consent obtained by the patients. Results: Thus far, we measured plasma concentration of tamoxifen and its metabolites for 158 pts among 198 pts genotyped. 59 pts (29.8%) carried CYP2D6*1/*1, 84 pts (42.4%) *1/*10 and 49 pts (24.7%) *10/*10. Other types were CYP2D6*1/*5 (8.6%), *5/*5 (1.0%), *1/*2×2 (2.5%). Pts with CYP2D6 *10/*10 (n=40) demonstrated significantly lower steady state plasma concentrations of BX and 4OH than those with other genotypes (n=118) (BX: 7.9 vs.19.2. ng/ml [95 % CI; 5.5–10.4 vs. 15.8–22.7 ng/ml] p<0.0001; 4OH: 1.5 vs. 2.8 ng/ml [95 % CI; 1.1–2.0 vs. 2.3–3.3 ng/ml] p<0.0001), whereas there were no differences with *1/*10 (n=64) vs. without *10 allele (n=54) (BX: 20.6 vs. 18.1 ng/ml; 4OH: 2.9 vs. 2.7 ng/ml). Basically no significant differences in BX/4OH or other compounds by various CYP2D6*2 ×2 and *5 alleles were observed. Conclusions: The steady state plasma concentrations of BX and 4OH were significantly low with CYP2D6 *10/*10 genotype, and their clinical implications need to be explored.(Supported by a grant NCC-0410590). No significant financial relationships to disclose.

Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2035-2035 ◽  
Author(s):  
M. L. Maitland ◽  
K. Moshier ◽  
J. Imperial ◽  
K. E. Kasza ◽  
T. Karrison ◽  
...  
Keyword(s):  
Steady State ◽  
Signaling Pathway ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Cancer Therapeutics ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway ◽  
State Plasma

2035 Background: Hypertension is a commonly reported toxicity of agents that inhibit the VEGF signaling pathway (VSP). This new class of cancer therapeutics has broad activity, but optimal dosing methods and integration into established treatment regimens could be enhanced by identification of reliable biomarkers. S, a new treatment for advanced renal cell carcinoma, is an orally available inhibitor of multiple VSP kinases including Raf-1 and VEGFR2. To characterize the chronicity and interindividual variability of BP responses to VSP inhibition we collected serial, standardized measures of BP and concurrent steady-state plasma concentrations ([plasma]) of S, from 30 patients (pts). Methods: Pts with advanced solid tumors, ECOG performance status < 2, and screening BP ≤ 140/90 mmHg on no more than one antihypertensive agent took 400mg S twice daily. Prior to therapy and at 3 time points after steady state [plasma] of drug was achieved, pts underwent 24-hour ambulatory BP monitoring with the SunTech Oscar PowerPack 2 (SunTech Medical, Morrisville, North Carolina). Readings were collected every 15 minutes during daytime hours and every 45 minutes overnight. Results: Unweigthed mean and standard deviations (sd) of systolic (SBP) and diastolic (DBP) 24-hr BP measurements were calculated for each pt. for the sessions pre-therapy and when steady state [plasma] S was reached (between days 6–10 after starting treatment). The differences in mean BPs between the two sessions were compared with (and p values reported for) paired t-tests. Regression analysis of [plasma] of S with either DBP or SBP, or change in DBP or SBP, with main effect and interaction terms for albumin, age, and sex revealed no significant correlation between S [plasma] and BP response. Conclusions: BP elevation is a biomarker for VSP inhibition. The known variability (coefficient of variation = 70%) in total S steady state plasma concentrations did not account for the observed variability in BP response. [Table: see text] [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document