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Pharmacokinetic Differences (pharmacokinetic + difference)
Selected AbstractsPopulation pharmacokinetics of ketanserin in pre-eclamptic patients and its association with antihypertensive responseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2005Lidwien M. Hanff Abstract Ketanserin is an antihypertensive drug that is increasingly being used parenterally in the treatment of pre-eclampsia. Because of lack of efficacy in a substantial part of our pre-eclamptic patients, we determined the plasma concentrations of ketanserin in 51 pre-eclamptic patients. Population pharmacokinetic parameters were assessed using the iterative two-stage Bayesian population procedure. The influence of individual pharmacokinetic parameters on antihypertensive response, expressed as the attainment of a diastolic blood pressure ,90 mmHg using ketanserin treatment, was analysed. Almost all plasma concentrations of ketanserin were in or above the therapeutic range. The individual pharmacokinetics of ketanserin in pre-eclamptic patients showed an accurate fit using a three-compartment model. The pharmacokinetic parameters in our pre-eclamptic population were a metabolic clearance (Clm) of 37.9 ± 10.86 L/h and volume of distribution (V1) of 0.544 ± 0.188 L/kg, which is comparable with data from healthy volunteers. Despite a considerable inter-individual variation, no correlation was found between differences in pharmacokinetic parameters and antihypertensive response. We conclude that therapeutic plasma levels can be obtained in pre-eclamptic patients with a fixed dosage schedule of ketanserin and differences in antihypertensive responses within a pre-eclamptic population cannot be attributed to pharmacokinetic differences. [source] Metabolic differences between Asian and Caucasian patients on clozapine treatmentHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007Mythily Subramaniam Abstract Objective To establish if there are ethnic differences in the various metabolic disturbances that are common with clozapine treatment. Method Forty subjects (20 Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for the study. Clozapine blood levels as well as fasting blood glucose, lipid levels, and liver function tests were established. Other clinical parameters such as blood pressure and Body Mass Index (BMI) were recorded for each patient. Results The mean clozapine dose was significantly higher in the Caucasian subjects (432.5,±,194.7,mg) as compared to the Asian subjects (175.6,±,106.9,mg) (p,<,0.001) while the mean weight-corrected dose for Asian patients was lower (3.0,±,1.9 and 5.0,±,2.1,mg/kg, respectively, p,=,0.005). There were, however, no ethnic differences in the mean plasma clozapine concentration (415.3,±,185.8,ng/ml in Caucasians and 417.1,±,290.8,ng/ml in Asians). BMI were significantly higher in Caucasians, as were the number of subjects with hypertension; levels of hepatic enzymes were higher in the Asian group. Conclusions Not only are there pharmacokinetic differences between Asian and Caucasian patients receiving clozapine, but there may also be differential emergence of certain metabolic abnormalities like hypertension and weight gain in these two ethnic groups. However, the effects of life style including diet and exercise cannot be excluded. Copyright © 2007 John Wiley & Sons, Ltd. [source] Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009J. Davis Abstract The objective of the study was to use the combined approach of gamma scintigraphy and pharmacokinetics, in order to understand the mechanisms explaining the pharmacokinetic differences observed for a modified release (MR) formulation, when administered either in the fed or fasted state. Ten healthy subjects were recruited into a randomized three period single dose study, each subject receiving UK-294,315 40 mg IR (fasted), 100 mg MR (fasted) or 100 mg MR (after a high fat meal). Cmax values were markedly higher for the MR tablet in the fed state versus fasted and mean residence time was about 3 h longer for fasted versus fed; there was little difference in apparent oral clearance. In the fasted state, average gastric emptying of the intact tablet occurred at 1.2 h postdose, with gastric emptying of intact tablet observed in all subjects. In the fed state, rapid disintegration of the MR tablet was observed by scintigraphy, with 7/9 subjects showing complete disintegration in the stomach. Complete disintegration occurred 10.1 h postdose in the fasted state versus 5.9 h after a high fat meal. The study showed that in the fed state, the MR tablet eroded more rapidly than in the fasted state, leading to an overall increase in the rate of absorption. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1568,1576, 2009 [source] Sirolimus pharmacokinetic differences between children and adultsPEDIATRIC TRANSPLANTATION, Issue 8 2006Raman Venkataramanan No abstract is available for this article. [source] Pharmacokinetics of anthraquinones in Xiexin decoction and in different combinations of its constituent herbsPHYTOTHERAPY RESEARCH, Issue 3 2009Dongming Yan Abstract Xiexin decoction (XXD), a classic pyretolysis formula, is composed of Rhei Rhizoma (DH), Radix Scutellaria (HQ) and Coptis Chinensis (HL) and is commonly used in the clinical setting. The aim of this study was to investigate the pharmacokinetic differences of the five anthraquinones in rats after oral administration of XXD and different combinations of its constituent herbs. Twenty rats were randomly divided into four groups and were administered one of the four extracts: DH, DH-HQ, DH-HL and XXD (DH-HQ-HL) via intragastric gavage. Anthraquinone concentrations in plasma were determined by an HPLC technique. Pharmacokinetic parameters were calculated from the plasma concentration,time data. Compared with DH alone, the DH-HL combination decreased Cmax of all five anthraquinones and AUC of four anthraquinones (except physcion), and the DH-HQ combination decreased AUC of aloe-emodin and Cmax of rhein. Finally, XXD increased AUC of all five anthraquinones compared with DH-HL combination. These results showed that the oral bioavailabilities of five anthraquinones were decreased significantly by combining DH with HL, whereas HQ weakened the effect of HL that inhibited the absorption of anthraquinones. Copyright © 2008 John Wiley & Sons, Ltd. [source] Randomized cross-over clinical trial of injectable vs. implantable depot testosterone for maintenance of testosterone replacement therapy in androgen deficient menCLINICAL ENDOCRINOLOGY, Issue 1 2010Carolyn Fennell Summary Background, Life-long testosterone replacement therapy (TRT) for younger men with organic androgen deficiency is best provided by depot testosterone (T) products. This study compared directly the two long-acting depot T products, subdermal T implants (TI) and injectable T undecanoate (TU) for maintenance of TRT. Design, setting and participants, Men with organic androgen deficiency (n = 38) undergoing regular TRT at an academic Andrology centre were recruited for a two period, randomized sequence, cross-over clinical trial without intervening wash-out period of TRT maintenance. Outcomes, For both depot T products, their pharmacokinetics and pharmacodynamics were evaluated using a range of androgen sensitive clinical, laboratory and quality of life measures as well as preference for ongoing treatment after experience of both products. Results, The two depot T products had distinct pharmacokinetics and were not bioequivalent. However, there were no consistent clinical differences in a comprehensive range of pharmacodynamic measures reflecting androgen effects on biochemistry and haematology, muscle mass and strength, and quality of life, mood and sexual function. The majority (91%) of participants chose TU over TI at study completion. Conclusion, Despite significant pharmacokinetic differences, the two depot T products are clinically interchangeable allowing for choice dependent on patient and physician delivery preference in practice but most patients preferred the injectable over the implantable form. [source] | ||||||||||