The previous version, ICD-10, had incorporated transsexualism, dual role transvestism, and gender identity disorder of childhood into its gender identity disorder category. It defined transsexualism as "[a] desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, ones anatomic sex, and a wish to have surgery and hormonal treatment to make ones body as congruent as possible with ones preferred sex." ICD-11 renamed Transexualism as Gender incongruence of adolescence or adulthood (HA60), and Gender identity disorder of childhood was renamed Gender incongruence of childhood (HA61). HA60 of the ICD-11 reads:Gender Incongruence of Adolescence and Adulthood is characterised by a marked and persistent incongruence between an individual´s experienced gender and the assigned sex, which often leads to a desire to ‘transition’, in order to live and be accepted as a person of the experienced gender, through hormonal treatment, surgery or other health care services to make the individual´s body align, as much as desired and to the extent possible, with the experienced gender. The diagnosis cannot be assigned prior the onset of puberty. [HA61 applies before puberty] Gender variant behaviour and preferences alone are not a basis for assigning the diagnosis.Historically, transsexualism has also been included in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM). With the DSM-5, transsexualism was removed as a diagnosis, and a diagnosis of gender dysphoria was created in its place.
History
Since the synthesis of 5-fluorouracil (5-FU) in 1957, fluoropyrimidines have been used to treat many types of cancer. Due to the drawbacks of 5-FU therapy, such as having to be administered over long periods of time via intravenous infusion and the development of resistance in tumors, more convenient and efficacious fluoropyrimidine therapy has been desired. The fluoropyrimidine component of this drug, trifluridine, was first synthesized in 1964 by Heidelberger et al.By the late 1960s, Phase I and Phase II clinical trials of intravenous trifluridine alone initially proved to be disappointing. Its pharmacokinetic profile during these clinical trials showed that the drug exhibited a very short half-life while in serum (12 minutes post-injection). Adjustments in the dosing regimen improved its effects in small studies, but the effect was short-lived.Researchers later found out that trifluridine, when taken orally, was broken down into the inactive metabolites 5-trifluoromethyluracil and 5-trifluoromethyl-2,4(1H,3,H)-pyrimidinedione (FTY) during its extensive first pass metabolism in the liver via the enzyme thymidine phosphorylase. It was then hypothesized that orally administered FTD concentrations could be increased and maintained if the drug was given with a thymidine phosphorylase inhibitor.Trifluridine/tipiracil was approved by the U.S. FDA in September 2015, and by the European Medicines Agency in April 2016. References
External links
"Tipiracil hydrochloride mixture with trifluridine". Drug Information Portal. U.S. National Library of Medicine.