Gender-related differences in the pharmacokinetics of opiates.

Abstract Previous studies have documented gender-related differences in a number of aspects of the pharmacology of opiates, including their analgesic activity, stimulative properties and generation of physical dependence. The current experiments were carried out with the aim to examine whether male–female differences exist in the blood and brain levels of opiates attained after their intraperitoneal injection to male and female Wistar rats. The tests were performed 5, 15, 45 and 120 min after the animal treatment with seized heroin. Gas chromatography–mass spectrometry (GC–MS) method was developed to quantitatively determine opiate alkaloids in blood and brain regions (known for their high concentration of μ-opiate receptors): cortex, brainstem, amygdala and basal ganglia. Maximal contents of opiates in blood of animals of both genders were found in the second measurement time (15 min), the values measured in the males being significantly higher, which suggests a faster passage of the opiates from blood to brain tissue in female animals. The highest content of opiates in the brain tissue of female animals was measured 15 min and with male animals 45 min after the treatment, which also indicates faster distribution of opiates from blood to brain in the female compared to male rats. The highest proportion of opiates was found in the basal ganglia of the animals of both genders. The obtained results offer the possibility of selecting this part of the brain tissue of both males and females as a representative sample for identifying and assessing contents of opiates.