Efficient Pharmacokinetic Modeling of Complex Clinical Dosing Regimens: The Universal Elementary Dosing Regimen and Computer Algorithm EDFAST

British Journal of Anaesthesia

2002

Section: Discussionmentioning

confidence: 99%

Concurrent ketamine and alfentanil administration: pharmacokinetic considerations

Edwards

Minto

British Journal of Anaesthesia

2002

“…Values of the maximum measured fentanyl concentration ( C max ) and the time at which C max occurred ( t max ) were obtained by inspection of the data. Additionally, the serial concentration‐time data for each subject at each dose were (adequately) fitted by a biexponential decay curve using Marquardt's weighted nonlinear regression procedure [11]. An exponential term describing a first‐order absorption process ( K a ) was added for the a.p.…”

Section: Methodsmentioning

confidence: 99%

“…The systemic pharmacokinetic properties of initial dilution volume ( V c ), mean total body clearance (CL T ), volume of distribution at steady state equilibrium ( V ss ) and slow half‐life ( t 1/2,z ) of fentanyl were calculated for i.v. administration using standard methods [11]. The area under the plasma fentanyl concentration vs time curve (AUC) was estimated by the linear trapezoidal method and extrapolated to infinity by adding the integrated terminal washout phase determined from the slow exponential term.…”

Section: Methodsmentioning

confidence: 99%

Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery

Woodhouse

Ward

et al. 1998

Brit J Clinical Pharma

Aims Pulmonary drug delivery is a promising noninvasive method of systemic administration. Our aim was to determine whether a novel breath-actuated, microprocessor-controlled metered dose oral inhaler (SmartMist TM , Aradigm Corporation) could deliver fentanyl in a way suitable for control of severe pain. Methods Aersolised pulmonary fentanyl base 100-300 mg was administered to healthy volunteers using SmartMist TM and the resultant plasma concentration-time data were compared with those from the same doses administered by intravenous (i.v.) injection in the same subjects. Results Plasma concentrations from SmartMist TM were similar to those from i.v. injection. Time-averaged bioavailability based upon nominal doses averaged #100%, and was >50% within 5 min of delivery. Fentanyl systemic pharmacokinetics were similar to those previously reported with no trends to dose-dependence from either route. Side-effects (e.g. sedation, lightheadedness) were the same from both routes. Conclusions Fentanyl delivery using SmartMist TM can provide analgetically relevant plasma drug concentrations. This, combined with its ease of noninvasive use and transportability, suggests a strong potential for field and domicilliary use, and for patient controlled analgesia without the need for i.v. cannulae.

“…administration of 2 and 4 mg morphine sulphate [10]. The serial plasma morphine concentration‐time data were fitted by a three compartment (central or plasma containing, peripheral rapidly equilibrating, peripheral slowly equilibrating) open model using Marquardt's algorithm implemented in EDFAST software on a personal computer [11]. The simulations are shown (Figure 1) for 1 mg of morphine sulphate.…”

Section: Methodsmentioning

confidence: 99%

The effect of duration of dose delivery with patient‐controlled analgesia on the incidence of nausea and vomiting after hysterectomy

Woodhouse

1998

Brit J Clinical Pharma

Aims Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients’ successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV. Methods Patients, who were receiving morphine for pain relief via patient‐controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded. Results Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P=0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups. Conclusions Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time‐course of emetic episodes between the two groups may be related to differences in the time‐course of central opioid receptor occupancy.