Biomaterial Database

The toxicity of tetrahydrobiopterin: acute and subchronic studies in mice. 1986

E M Lewandowski, and A B Combs, and K Folkers

Tetrahydrobiopterin (BH4) is presently being employed in clinical trials for the therapy of various neurological disorders. The toxicity of BH4 in mice was analyzed by acute and subchronic intraperitoneal and acute oral survival studies. Organ weight analysis and histopathology were performed after acute and subchronic i.p. administration. The effect of probenecid on BH4 toxicity was also tested. An LD50 of approximately 260 mg/kg was obtained from acute (14-day) intraperitoneal survival studies. A dose-dependent increase in kidney weights and histopathologic evidence of acute toxic tubular necrosis were noted in acute i.p. studies. Acute oral administration of up to 1318 mg/kg BH4 did not cause any significant morbidity or mortality, nor did subchronic (92-day) i.p. administration of 10 or 50 mg/kg BH4. Probenecid pretreatment did not decrease the toxicity of BH4. The importance of further evaluation of the potential toxicity of tetrahydrobiopterin in clinical utilization is emphasized.

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007683	Kidney Tubular Necrosis, Acute	Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.	Lower Nephron Nephrosis,Acute Kidney Tubular Necrosis,Lower Nephron Nephroses,Nephron Nephroses, Lower,Nephron Nephrosis, Lower,Nephroses, Lower Nephron,Nephrosis, Lower Nephron
D007928	Lethal Dose 50	The dose amount of poisonous or toxic substance or dose of ionizing radiation required to kill 50% of the tested population.	LD50,Dose 50, Lethal
D008297	Male		Males
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011339	Probenecid	The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.	Benecid,Benemid,Benuryl,Pro-Cid,Probecid,Probenecid Weimer
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D005260	Female		Females
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia