Kinetics of buccal absorption of amphetamines

Abstract

The buccal absorption of amphetamine, methylamphetamine and dimethylamphetamine in solutions at pH 8.16 and 9.18, was measured in man after 1,2, 3,4, 5 and 10 min. The recovery of the drugs from the buccal membrane after uptake was also measured by washing out the mouth for varying times with buffer solutions. An analogue computer model of the biological system was used and the kinetic parameters for the buccal absorption of the amphetamines were calculated.ECENTLY, the importance of examining the kinetics of drug transfer R between aqueous and organic phases has been emphasized (Doluisio & Swintosky 1964; Pemn 1967). These authors have devised various in vitro systems which allow rate of partition studies to be made, but as with partition coefficient experiments, rate of partition is profoundly influenced by the nature of the organic phase. Since these in vitro systems are intended to be models for the behaviour of drugs in various physiological functions i.e., gastrointestinal absorption, the success of the interpretation of the behaviour of a drug will depend on the extent to which the organic phase chosen simulates in vivo lipid membranes.To overcome this major disadvantage in currently available in v i m partition systems, the buccal absorption of drugs has been proposed as an in vivo model system for the study of drug transfer across physiological membranes (Beckett & Triggs, 1967). A description of the kinetics of the buccal absorption of three chemically related drugs, amphetamine, methylamphetamine and dimethylamphetamine is now presented. EXPERIMENTAL-BUCCAL ABSORPTION MEASUREMENTSApparatus. Perkin-Elmer F 11 Gas Chromatograph. Dynacap pH Meter.Bufler solutions. Potassium hydrogen phthalate (0-05 M) pH 4-00. Sodium tetraborate (0.05 M) pH 9.18. Sorensens phosphate buffer pH 8.16.Drug solutions. Solutions of the drugs amphetamine, methylamphetamine and dimethylamphetamine were prepared in the buffers of pH 8. 16 and 9.18 such that 25 ml contained the equivalent of 1 mg drug base.Male volunteers aged 20-40, who produced only small volumes of saliva, were used. A drug solution (25 ml) was introduced into the subject's mouth for 1, 2, 3, 4, 5 and 10 min. After each time the solution was expelled, diluted to a suitable volume and analysed for drug content.

Drug recovery following buccal absorption of propranolol.

“…Later work has clearly demonstrated by back-partitioning into freshly-introduced buffer solution that drugs may be recovered from the buccal mucosa (Beckett, Boyes & Triggs, 1968;Beckett & Pickup, 1975;Temple & Schesmer, 1978;Davis & Johnston, 1979), which is consistent with the hypothesis that passive buccal absorption of drugs is a reversible process.…”

Oral absorption and secretion of drugs.

“…More recently, literature describing the reliability of drug absorption through the oral mucosa was reviewed by Gibaldi & Kanig (1965 (Beckett, Boyes & Triggs, 1968;Beckett & Moffat, 1970;Beckett & Moffat, 1971). Others used some of these data to demonstrate that the octanol-water partition coefficient was an important parameter in determining buccal absorption (Lien, Koda & Tong, 1971).…”

Treatment of Narcolepsy with Methamphetamine

“…Our estimations of half-life, which were based on the linear drop in serum levels between the morning and afternoon measurements, averaged 22.0 hours. We also estimated half-life by fitting the four sets of morning and afternoon serum levels to absorption-elimination curves that peaked 2.5 hours after ingestion, because previously published pharmacokinetic data (29) indicate that methamphetamine reaches peak serum levels 2-3 hours after ingestion. These curve fittings resulted in an average half-life estimate of 15.9 hours, which is in contrast to the 4-5 hour figure cited by the manufacturer (19).…”