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Biomedical subjects

M Southam

Publications and source records attributed to M Southam.

6 recordsLinked to original sources
PubMed1999

Reproducible fentanyl doses delivered intermittently at different time intervals from an electrotransport system.

The electrotransport transdermal fentanyl system (ET [fentanyl]), uses a small electrical current to enhance delivery of fentanyl to systemic circulation. Intermittent doses can be administered by periodic application of the current. The purpose of this study was to compare the effects of the frequency of intermittent drug delivery by ET (fentanyl) and compare the drug delivery to systemic circulation by ET (fentanyl) with intravenous administration. The topical safety was also determined for the ET (fentanyl) system. Nine adult male volunteers completed this three-treatment, randomized, 24-h, crossover study. ET (fentanyl) treatments with 200 microA direct current applied for 30 min at frequent (hourly) or infrequent (4-hourly) intervals over a 24-h period were compared. Also, the drug delivery to systemic circulation from ET (fentanyl) was compared with intravenous fentanyl 75 microg infused over 30 min every 4 h over a 24-hour period. The mean serum fentanyl concentration achieved with the hourly ET (fentanyl) regimen was higher than that for the 4-hourly ET (fentanyl) regimen as expected from the higher frequency of drug doses. The amount of fentanyl delivered estimated per dose from the ET (fentanyl) system using the iv fentanyl treatment as the reference was similar for the two ET regimens throughout the dosing period. This indicates consistent drug delivery regardless of the frequency of ET dosing. The majority of subjects reported either no, or barely perceptible, erythema 24 h after removal of the system.

Administration, Cutaneous↗
PubMed1998

Effect of current density on pharmacokinetics following continuous or intermittent input from a fentanyl electrotransport system.

The pharmacokinetics of fentanyl were determined in two open-label crossover studies following 24-h periods of delivery by an electrotransport transdermal system (E-TRANS [fentanyl] system) in young healthy male volunteers. A direct current was applied continuously in study 1 (at 50, 100, and 200 microA; surface area = 5 cm2; n = 8), but in study 2 it was limited to the first 20 min of each hour (at 150, 200, and 250 microA; surface area = 2 cm2; n = 12). The opioid effects of fentanyl were blocked with naltrexone administered every 12 h. With increasing electrical current, the increase in serum fentanyl concentration, amount absorbed, and AUC values were proportional in study 2 but not in study 1. It is hypothesized that the lack of proportionality in study 1 is due to lower current density (microA/cm2) in this study. It appears that for fentanyl, the current density should be about 75 microA/cm2 or greater for a linear relation between current and amount absorbed as seen in study 2. Compared with intravenously infused fentanyl, the serum concentrations resulting from E-TRANS (fentanyl) system application revealed a slightly dampened rate of increase (stratum-corneum barrier effect) and decrease in serum concentrations, and a similar intersubject variability in fentanyl AUC values. Fentanyl pharmacokinetics with either E-TRANS (fentanyl) or intravenous infusion were time-invariant over a 24-h application period, with similar mean half-life values (about 15-18 h). E-TRANS (fentanyl) administration (either continuous or intermittent input) was safe and well tolerated. Adverse effects were mild to moderate; they consisted mainly of local erythema and pruritus (which resolved in most patients within 24 h after system removal) and occasional opioid effects.

Adult↗
PubMed1992

System functionality and physicochemical model of fentanyl transdermal system.

Fentanyl is an opioid traditionally administered by infusion or injection and more recently in a rate-controlled transdermal dosage form. This system is a four-layer laminate on a protective liner. A backing layer seals and protects the drug reservoir, the source for continuous delivery of fentanyl. A membrane controls the release rate of fentanyl from the system. An adhesive layer attaches the system to skin and releases an initial loading dose of fentanyl. The rate of fentanyl delivery through skin is determined by the system and the skin at the application site. The release rate from the system is approximated by Fick's first law of diffusion and is controlled by the rate-controlling membrane. A complete simulation model that combines both in vitro release data and the pharmacokinetic model has been developed and used to show the influence of various physiologic and system variables on serum fentanyl concentrations.

Administration, Cutaneous↗