EFFECT OF CONTINUOUS AND MULTIPLE DOSES OF 5-AMINOLEVULINIC ACID ON PROTOPORPHYRIN-IX CONCENTRATIONS IN THE RAT UTERUS

The objective of the present study was to determine if the concentrati on of protoporphyrin IX (PpIX) in the rat endometrium could be increas ed by administering 5-aminolevulinic acid (ALA) in multiple doses or b y continuous infusion. The effect of pH, temperature and time in solut ion on the stability of ALA were also investigated. Estrogen-filled si lastic capsules were implanted subcutaneously into ovary intact female rats (200-225 g) (n=66). On the third day of hormonal priming, ALA (1 0 mg or 25 mg) dissolved in saline and adjusted to a pH of 5-5.5 was a dministered intrauterine either as a single bolus or as two injections 3 hours apart (n = 10), A fifth group of rats was infused with 25 mg ALA over a 12 hour period using an osmotic minipump (n = 6), In a seco nd experiment, ALA ( 25 mg) was injected immediately after being disso lved in saline (pH 2) (n = 16) or after incubation at 37 degrees C for 12 hour (pH 2) (n = 7), PpIX was then extracted from the endometrium and myometrium using a 1:1 methanol/perchloric acid solution and quant ified spectrofluorometrically. A dose-response relationship was observ ed between in and 25 mg of ALA and endometrial PpIX concentrations. Ho wever, no differences in endometrial PpIX concentrations were detected between rats administered ALA either as a single bolus eras two doses . Continuous infusion of 25 mg of ALA resulted in statistically lower endometrial PpIX concentrations compared to 25 mg ALA injected either as a single bolus or as two injections. Neither pH, temperature, nor t ime in solution affected ALA-induced PpIX accumulation, We conclude th at the simplest way of achieving the highest PpIX concentration in the rat endometrium in vivo is to administer a bolus injection of 25 mg o f ALA. (C) 1997 Elsevier Science S.A.