Research
In modern times, clinical study of sexual problems is usually dated back no earlier than 1970 when Masters and Johnsons Human Sexual Inadequacy was published. It was the result of over a decade of work at the Reproductive Biology Research Foundation in St. Louis, involving 790 cases. The work grew from Masters and Johnsons earlier Human Sexual Response (1966). Prior to Masters and Johnson, the clinical approach to sexual problems was largely derived from Sigmund Freud. It was held to be psychopathology and approached with a certain pessimism regarding the chance of help or improvement. Sexual problems were merely symptoms of a deeper malaise, and the diagnostic approach was from the psychopathological viewpoint. There was little distinction between difficulties in function and variations nor between perversion and problems. Despite work by psychotherapists such as Balint sexual difficulties were crudely split into frigidity or impotence, terms which acquired negative connotations in popular culture. Human Sexual Inadequacy moved thinking from psychopathology to learning; psychopathological problems would only be considered if a problem did not respond to educative treatment. Treatment was directed at couples, whereas before partners would be seen individually. Masters and Johnson believed that sex was a joint act, and that sexual communication was the key issue to sexual problems, not the specifics of an individual problem. They also proposed co-therapy, with a pair of therapists to match the clients, arguing that a lone male therapist could not fully comprehend female difficulties.
Linear increases in circulating naltrexone and 6β-naltrexol concentrations occur over an oral dose range of 50 to 200 mg. Naltrexone does not appear to be accumulated with repeated once-daily oral administration and there is no change in time to peak concentrations with repeated administration.The plasma protein binding of naltrexone is about 20% over a naltrexone concentration range of 0.1 to 500 μg/L. Its apparent volume of distribution at 100 mg orally is 16.1 L/kg after a single dose and 14.2 L/kg with repeated doses.Naltrexone is metabolized in the liver mainly by dihydrodiol dehydrogenases into 6β-naltrexol (6β-hydroxynaltrexone). Levels of 6β-naltrexol are 10- to 30-fold higher than those of naltrexone with oral administration due to extensive first-pass metabolism. Conversely, 6β-naltrexol exposure is only about 2-fold higher than that of naltrexone with intramuscular injection of naltrexone in microspheres (brand name Vivitrol). 6β-Naltrexol is an opioid receptor antagonist similarly to naltrexone and shows a comparable binding profile to the opioid receptors. However, 6β-naltrexol is peripherally selective and crosses into the brain much less readily than does naltrexone. In any case, 6β-naltrexol does still show some central activity and may contribute significantly to the central actions of oral naltrexone. Other metabolites of naltrexone include 2-hydroxy-3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxynaltrexone. Following their formation, the metabolites of naltrexone are further metabolized by conjugation with glucuronic acid to form glucuronides.