Pharmacokinetics of physostigmine in man following a single application of a transdermal system.

Abstract

1 The pharmacokinetics of physostigmine were investigated in a three-way crossover design in six healthy, male volunteers comparing a physostigmine transdermal system (PTS), an oral solution and an i.v. infusion. 2 A single application of the patch over 24 h produced detectable plasma drug concentrations after a mean lag-time of 4 h. Thereafter, the drug was absorbed continuously from the PTS and putative therapeutic plasma concentrations were measured over approximately 18 h. 3 A mean absolute bioavailability of 36% was determined for the transdermal system and 3% for the oral solution. In comparison with the oral solution, interindividual variability of pharmacokinetics was less with the PTS. 4 The mean amount of physostigmine released from the transdermal system after 24 h was 5.7 mg. Because of extensive metabolism, only 2.2 mg of physostigmine were detected systemically. 5 After removing the PTS, the mean apparent half-life of elimination was 4.9 h, compared with 0.5 h for the i.v. infusion. This indicates continued drug absorption from a skin depot. 6 Physostigmine was well tolerated by the volunteers. With the PTS, a mild erythema was observed at the area of application, disappearing within a few hours.

Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic, pharmacodynamic and in vitro/in vivo correlation evaluation

“…T max , C max , AUC 0-t , MRT and F) were determined and summarized in Table 4. Usually, transdermal patches could obtain an absolute bioavailability (F) of about 40-50% (Kivistö et al, 1994;Walter et al, 1995). The F of the developed patch in our study was 42.53%, which was within the range and thus acceptable.…”

Biologically active components of Physostigma venenosum

“…Most often octanesulfonic acid was employed; however, acetic acid, formic acid, phosphoric acid, heptanesulphonic acid and low pH buffer have also been used. Typically, an acid is added to the aqueous phase, although some report adding a small amount of acid to the organic solvents as well [46]. Walter et al [46] described their mobile phase as consisting of phosphate acid and acetonitrile (75:25, pH 4.0) containing heptanesulphonic acid.…”

“…Commonly used extraction solvents in liquid-liquid extraction (LLE) schemes for physostigmine and/or its metabolites, includes diethyl ether [40][41][42]45], methyl tert-butyl ether [20,43,46], chloroform [47,48] and methylene chloride [44]. There is little to distinguish these solvents in terms of their extraction power.…”

“…However, the LLE clean-up procedure is labor intensive and time consuming and some involve extraction of physostigmine into an organic phase and then back-extraction into an acidified aqueous phase [43,44,46].…”

Preparation, characterization, and in vitro evaluation of physostigmine-loaded poly(ortho ester) and poly(ortho ester)/poly(d,l-lactide-co-glycolide) blend microspheres fabricated by spray drying

“…Recently, scientists have also discovered the potential benefit of physostigmine in treating the symptom of Alzheimer's disease [27,28]. The therapeutic use of physostigmine is limited by biological constraints such as short elimination half-life, narrow effective dose range, poor in vivo stability and low bioavailability [29,30]. A controlled release device of physostigmine is desirable as it can avoid the need of multiple doses, improve drug stability and release physotigmine in a controlled fashion.…”