People aged 70–81, relative to people aged 18–26, have decreased renal clearance of primidone, phenobarbital, and PEMA, in ascending order of significance, and that there was a greater proportion of PEMA in the urine. The clinical significance is unknown. The percentage of primidone converted to phenobarbital has been estimated to be 5% in dogs and 15% in humans. Work done twelve years later found that the serum phenobarbital 0.111 mg/100 mL for every mg/kg of primidone ingested. Authors publishing a year earlier estimated that 24.5% of primidone was metabolized to phenobarbital. However, the patient reported by Kappy and Buckley would have had a serum level of 44.4 mg/100 mL instead of 8.5 mg/100 mL if this were true for individuals who have ingested large dose. The patient reported by Morley and Wynne would have had serum barbiturate levels of 50 mg/100 mL, which would have been fatal. History
Primidone is a congener of phenobarbital where the carbonyl oxygen of the urea moiety is replaced by two hydrogen atoms. The effectiveness of Primidone for epilepsy was first demonstrated in 1949 by Yule Bogue. He found it to have a similar anticonvulsant effect to phenobarbitol, but more specific, i.e. with fewer associated sedative effects.It was brought to market a year later by the Imperial Chemical Industry (ICI), now known as AstraZeneca in the United Kingdom and Germany. In 1952, it was approved in the Netherlands.Also in 1952, Drs.
Telotristat ethyl (USAN, brand name Xermelo) is a prodrug of telotristat, which is an inhibitor of tryptophan hydroxylase. It is formulated as telotristat etiprate — a hippurate salt of telotristat ethyl.On February 28, 2017, the U.S. Food and Drug Administration (FDA) approved telotristat ethyl in combination with somatostatin analog (SSA) therapy for the treatment of adults with diarrhea associated with carcinoid syndrome that SSA therapy alone has inadequately controlled. Telotristat ethyl was approved for use in the European Union in September 2017.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Pharmacology
Telotristat is an inhibitor of tryptophan hydroxylase, which mediates the rate-limiting step in serotonin biosynthesis. Adverse effects
Common adverse effects noted in clinical trials include nausea, headache, elevated liver enzymes, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite, and fever. Constipation is also common, and may be serious or life-threatening (especially in overdose). Formulations
It is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl. References
Further reading
Kulke MH, ODorisio T, Phan A, Bergsland E, Law L, Banks P,  et al. (October 2014). "Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide". Endocrine-Related Cancer. 21 (5): 705–14. doi:10.1530/ERC-14-0173. PMC 4295770. PMID 25012985. External links
"Telotristat ethyl". Drug Information Portal. U.S. National Library of Medicine. "Telotristat etiprate". Drug Information Portal. U.S. National Library of Medicine.