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Order Elimination (order + elimination)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Order Elimination

  • first order elimination
    		•

    Selected Abstracts

    Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses

    JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
    R. L. LINARDI
    Methadone hydrochloride is a synthetic ,-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (Vd/F) and short elimination half-life (t1/2). The mean of the estimated t1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated Cmax (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively. [source]

    Clonidine disposition in children: a population analysis

    PEDIATRIC ANESTHESIA, Issue 6 2007
    AL Potts
    Background:, There are few data describing clonidine population pharmacokinetics in children (0,15 years) despite common use. Current paediatric data, described in terms of elimination half-life or Cmax and Tmax, poorly explain variability in drug responses among individuals representative of those in whom the drug will be used clinically. Methods:, Published data from four studies investigating clonidine PK after intravenous, rectal and epidural administration (n = 42) were combined with an open-label study undertaken to examine the pharmacokinetics of IV clonidine 1,2 ,g·kg,1 bolus in children after cardiac surgery (n = 30, EC approval granted). A population pharmacokinetic analysis of clonidine time-concentration profiles (380 observations) was undertaken using nonlinear mixed effects modelling. Estimates were standardised to a 70 kg adult using allometric size models. Results:, Children had a mean age of four (SD 3.6 years, range 1 week,14 years) year and weight 17.8 (SD 12.6, range 2.8,60 kg). A two compartment disposition model with first order elimination was superior to a one compartment model. Population parameter estimates (between subject variability) were clearance (CL) 14 (CV 28.3%) 1 h,1·70 kg,1, central volume of distribution (V1) 56.7 (67.5%) l·70 kg,1, inter-compartment clearance (Q) 143 (19.1%) l h,1 70 kg,1 and peripheral volume of distribution (V2) 123 (72.8%) l.70kg,1. Clearance at birth was 4.7 l·h,1·70kg,1 and matured with a half-time of 25.5 weeks to reach 85% adult rate by 1 year of age. The volumes of distribution, but not clearance, were increased after cardiac surgery (V1 180%, V2 117%). There was a lag time of 2.6 (CV 64%) min before absorption began in the rectum. The absorption half-life from the epidural space was slower than that from the rectum 1.04 (CV31%) h vs 0.28 (CV24%) h. The relative bioavailability of epidural and rectal clonidine was unity (F = 1). Conclusions:, Clearance in neonates is approximately one third that described in adults, consistent with immature clearance pathways. Maintenance dosing, which is a function of clearance, should be reduced in neonates and infants when using a target concentration approach. [source]

    Pharmacokinetic monitoring of intravenous cyclosporine A in pediatric stem-cell transplant recipients.

    PEDIATRIC TRANSPLANTATION, Issue 4 2009
    The trough level is not enough
    Abstract:, In order to monitor CsA serum levels after SCT, trough levels (C0) are widely used. The aim of this study was to estimate the population and individual PK parameters for patients receiving intravenous CsA after SCT. In 27 pediatric patients after SCT receiving CsA (3 mg/kg/day) every 12 h, a total of 289 CsA concentrations was obtained. To describe the PK parameters of CsA, a two-compartment model with first order elimination was used. Covariate analysis identified body weight, age, and the co-administration with itraconazole and tobramycine as factors influencing the Cl. The statistical comparison of AUC, trough level, and C2 indicates a correlation between AUC and C2, but no correlation between the AUC and C0, r = 0.24 (p = 0.146) vs. r = 0.526 (p = 0.000692), respectively. Our results underscore the fact that CsA trough levels do not reflect the drug exposure in patients receiving intravenous CsA after SCT. By contrast, CsA blood levels measured 2,6 h after CsA infusion showed a better correlation with the AUC. Our data provide new information to optimize the balancing act between GvHD-prophylaxis, graft vs. leukemia effect, and CsA side-effects after SCT. [source]

    Population pharmacokinetics of oral diclofenac for acute pain in children

    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008
    Joseph F. Standing
    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range. , Diclofenac is frequently used ,off-label' in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5,2.5 mg kg,1). There is currently no licensed oral paediatric formulation of diclofenac. WHAT THIS STUDY ADDS , Using a new diclofenac oral suspension, a dose of 1 mg kg,1 in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses. AIMS To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml,1) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children. METHODS Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg,1 dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults. RESULTS A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and VD/F were 53.98 l h,1 70 kg,1 and 4.84 l 70 kg,1 respectively. Allometric size models appeared to predict adequately changes in CL and VD with age. Of the simulated doses investigated, 1 mg kg,1 gave paediatric AUC(0,12 h) to adult 50 mg AUC(0,12 h) ratios of 1.00, 1.08 and 1.18 for ages 1,3, 4,6 and 7,12 years respectively. CONCLUSIONS This study has shown 1 mg kg,1 diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses. [source]