Relationship of Prolactin Concentrations to Steady-state Plasma Concentrations of Aripiprazole in Schizophrenia Patients

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).

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Relationships among duration of infusion, dose, dosing interval, and steady-state plasma concentrations during intermittent intravenous infusions: Studies with metronidazole

Journal of Pharmacokinetics and Biopharmaceutics ◽

10.1007/bf01059286 ◽

1986 ◽

Vol 14 (1) ◽

pp. 95-106 ◽

Cited By ~ 2

Author(s):

Dominic A. Uccellini ◽

Denis J. Morgan ◽

Kenneth Raymond

Keyword(s):

Steady State ◽

Plasma Concentrations ◽

Dosing Interval ◽

Intravenous Infusions ◽

State Plasma

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

Clinical Pharmacokinetics ◽

10.2165/00003088-199120030-00005 ◽

1991 ◽

Vol 20 (3) ◽

pp. 237-244 ◽

Cited By ~ 20

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

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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.634 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 634-634 ◽

Cited By ~ 1

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2035 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2035-2035 ◽

Cited By ~ 19

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]

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