Abstract:
AIMS:The aim of this analysis was to develop a population pharmacokinetic model for Emfilermin (recombinant human leukaemia inhibitory factor, r-hLIF) following subcutaneous administration to healthy postmenopausal women and to infertile patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS:Data from three studies, a single and a repeat dose Phase I study in postmenopausal women as well as a proof of concept study in patients undergoing in vitro fertilization and embryo transfer were combined and analyzed. The structural pharmacokinetic model was developed using the rich data from the Phase I studies and the full pharmacostatistical model was then derived using all the data. RESULTS:The pharmacokinetics of r-hLIF after repeated subcutaneous administration were described by a one-compartment disposition model with a zero order input. The duration of the absorption phase was short (0.8 h) and invariant. The apparent clearance in postmenopausal women was 57 l h(-1) (CV = 17%). In in vitro fertilization and embryo transfer patients, the apparent clearance was decreased by 35% compared with postmenopausal women. The apparent volume of distribution was 235 l (interindividual CV = 28%) and exhibited an interoccasion variability of 23%. It increased (for weight above 62 kg) or decreased (for weight below 62 kg) by 29% for every 10 kg body weight. The median posthoc estimates of apparent clearance and volume of distribution and their variability were consistent with the population estimates. In postmenopausal women, the results were consistent with those obtained by noncompartmental analysis. The residual variability on r-hLIF serum concentrations was 20%. CONCLUSIONS:The pharmacokinetics of r-hLIF after repeated SC administration were described by a one compartment disposition model, with zero order input, in postmenopausal women and those undergoing IVF or intracytoplasmic sperm injection and embryo transfer. Absorption of r-hLIF was rapid as was its subsequent clearance. The apparent volume of distribution of r-hLIF was moderate to high, depended on body weight and showed interoccasion variability.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Goggin T,Nguyen QT,Munafo Adoi
10.1111/j.1365-2125.2003.02064.xkeywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
576-85issue
5eissn
0306-5251issn
1365-2125pii
BCP2064journal_volume
57pub_type
临床试验,杂志文章,随机对照试验abstract::1 Haemodynamic effects of cigarette smoking before and during chronic treatment with propranolol and metoprolol were studied in 16 patients with essential hypertension. 2 Smoking of cigarettes induced an increase in blood pressure of the same degree in all experimental sessions. Heart rate increased by 16 beats/min du...
journal_title:British journal of clinical pharmacology
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abstract::1 The effect of low dose steady state warfarin (0.2 mg and 1 mg daily) on clotting factor activity and vitamin K1 metabolism was studied in seven healthy volunteers. 2 Steady state plasma warfarin concentrations were 41-99 ng ml-1 for the 0.2 mg dose and 157-292 ng ml-1 for the 1 mg dose. 3 There was a significant pro...
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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