title: Concentrations of trimethoprim and sulfamethoxazole in cerebrospinal fluid and serum in mares with and without a dimethyl sulfoxide pretreatment.
abstract: Each of seven mares was given an intravenous (IV) injection of 40% dimethyl sulfoxide (DMSO) at a dosage of 1 g/kg, over 35 min, immediately followed by a single IV injection of a trimethoprim (TMP) and sulfamethoxazole (SMZ) combination (SMZ 83%, TMP 17%) at a combined dosage of 44 mg/kg (7.48 mg/kg TMP; 36.52 mg/kg SMZ). Each horse served as its own control and was alternately treated with an identical dose of TMP-SMZ treatment alone at least seven days following or preceding the DMSO and TMP-SMZ treatment. Serum and cerebrospinal fluid (CSF) concentrations of TMP and SMZ were measured over a six hour period. Dimethyl sulfoxide treatment caused no significant difference in the mean serum concentration of SMZ or in the mean CSF concentrations of TMP or SMZ. The mean serum concentration of TMP was significantly (p less than 0.05) increased at the two, four and six hour sampling time in the mares receiving pretreatment with DMSO. The clearance of TMP was also significantly (p less than 0.05) decreased from 675 mL/h/kg to 327 mL/h/kg by DMSO administration. Concentrations of TMP and SMZ in the CSF in both treatment groups exceeded the minimum inhibitory concentrations for many common bacterial pathogens of equine origin. In addition, CSF concentration of TMP exceeded the serum concentrations required for 50% inhibition of dihydrofolate reductases of protozoan origin. Serum TMP and SMZ concentration were similar to those reported to be effective against Toxoplasma gondii in in vitro studies on the killing or inhibition of the organism.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0126.
authors.forename: S L
authors.initials: SL
authors.lastname: Green
authors.forename: I G
authors.initials: IG
authors.lastname: Mayhew
authors.forename: M P
authors.initials: MP
authors.lastname: Brown
authors.forename: R R
authors.initials: RR
authors.lastname: Gronwall
authors.forename: G
authors.initials: G
authors.lastname: Montieth
mesh_terms: D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004906:Erythrocyte Count / Q000662:veterinary; D005260:Female; D006736:Horses / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D007958:Leukocyte Count / Q000662:veterinary; D013420:Sulfamethoxazole / Q000097:blood / Q000134:cerebrospinal fluid*; D014295:Trimethoprim / Q000097:blood / Q000134:cerebrospinal fluid*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole; D004121:Dimethyl Sulfoxide