Biomedical subjects

T S Tracy

Publications and source records attributed to T S Tracy.

6 recordsLinked to original sources

PubMed1992

The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Adult↗

PubMed1992

Ability of nifedipine to prolong parturition in rats.

Rats were randomly assigned to treatments: (i) no surgery control; (ii) saline control; (iii) 0.25, 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1; or (iv) 5.0 micrograms ritodrine kg-1 min-1. All drug treatments increased the interval between pup deliveries compared with the no surgery and saline controls. Apparent complete tocolysis was observed in 20, 60, 80 and 80% of the animals receiving 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1 or 5.0 micrograms ritodrine kg-1 min-1, respectively. A positive pharmacodynamic relationship was observed for the nifedipine doses. Analysis of pup viability showed no statistically significant difference among treatments. Treatment with 2.0 micrograms nifedipine kg-1 min-1 gave a delay in pup delivery comparable to that with ritodrine.

Animals↗

PubMed1991

Determination of the epimeric composition of ibuprofenyl-CoA.

Ibuprofen [racemic2-(4-isobutylphenyl)propionic acid] is a 2-arylpropionic acid nonsteroidal anti-inflammatory drug which undergoes unidirectional, R to S chiral inversion in vivo. It has been proposed that this chiral inversion phenomenon occurs via a coenzyme A (CoA) thioester intermediate. To characterize the formation and metabolism of this metabolic intermediate, ibuprofenyl-CoA, reference standards were needed and thus the CoA derivatives of (R)-, (S)-, and racemic ibuprofen were chemically synthesized. An HPLC assay employing a C18 reverse-phase column was developed to quantitate "total" ibuprofenyl CoA. Samples collected from this assay were then analyzed for ibuprofenyl-CoA epimeric composition by chiral chromatography employing a Chiral-AGP alpha 1-acid glycoprotein column. The applicability of these methods was demonstrated by assessing (R)- and (S)-ibuprofenyl-CoA hydrolysis and epimerization following incubation with rat liver homogenates. Rat liver homogenate catalyzed the complete and rapid epimerization of ibuprofenyl-CoA and the rate constants for (R)- and (S)-ibuprofenyl-CoA hydrolysis were equal. ATP and CoA were found to inhibit rat liver-catalyzed ibuprofenyl-CoA hydrolysis by 70-80% with no effect on epimerization. Additionally, it was demonstrated that traditional indirect ibuprofenyl-CoA assays which employ basic hydrolysis result in erroneous epimeric ratio determinations due to chemical epimerization.

Acyl Coenzyme A↗

PubMed1989

Nitroglycerin delivery through a polyethylene-lined intravenous administration set.

Adsorption and delivery of nitroglycerin through a new polyethylene-lined (PEL) i.v. administration set was compared with adsorption and delivery through an identical set composed of polyvinyl chloride (PVC) rather than PEL tubing. The new delivery system consisted of PEL tubing, a transparent PVC chamber, and a silastic segment for insertion in a peristaltic pump. Nitroglycerin was prepared in concentrations of 50, 125, and 200 micrograms/mL in 0.9% sodium chloride injection and run through both administration sets at flow rates of 12 and 60 mL/hr. Samples were obtained at 0, 0.5, 1, 2,4, and 8 hours from each of three sites: bottle, junction before silastic segment, and distal end of tubing. Nitroglycerin content was assayed using a modified high-performance liquid chromatography technique. A slight but significant average loss of nitroglycerin (2.3 +/- 9.3%) was observed at the distal end with the PEL set, whereas the PVC set showed a significant average nitroglycerin loss of 39.7 +/- 12.7% at the distal end. These differences were independent of infusion rate, nitroglycerin concentration, or time of sampling. Flow rate, concentration, and time had no significant effect on nitroglycerin adsorption with the PEL set, but all three had a significant effect on nitroglycerin adsorption with the PVC set. An unexpected finding was the approximately 14% loss of nitroglycerin from the admixture bottle over time. This phenomenon, which has been observed by other investigators, needs further investigation to determine its cause. It appears that a partially PVC-based administration set should provide consistent delivery of i.v. nitroglycerin to the patient.

Chemistry, Pharmaceutical↗

PubMedDate not supplied

Calcium modulators: future agents, future uses.

The calcium modulators have been a significant therapeutic advancement for the treatment of angina. Structural analogs of verapamil and nifedipine have been synthesized, as have structurally unique compounds. As the role of calcium in body processes is further elucidated, the efficacy of the calcium modulators is being evaluated for numerous disorders. It is anticipated that the newly synthesized compounds will have specificity toward particular body processes, thus providing efficacy with minimal side effects.

Asthma↗

PubMedDate not supplied

Metabolic inversion of (R)-ibuprofen. Epimerization and hydrolysis of ibuprofenyl-coenzyme A.

Ibuprofen [(racemic)2-(4-isobutylphenyl)propionic acid] has been proposed but not directly demonstrated to undergo unidirectional inversion from the (R)- to the (S)-configuration via a coenzyme A (CoA) thioester intermediate. Chemically synthesized (R)- and (S)-ibuprofenyl-CoA, and rat and human liver homogenates were used to investigate the relative rates of ibuprofenyl-CoA epimerization and hydrolysis. Rat whole liver homogenate completely epimerized (R)- or (S)-ibuprofenyl-CoA, whereas hydrolysis of this intermediate occurred at a much slower rate. Rat liver mitochondria was the most efficient at both epimerizing and hydrolyzing ibuprofenyl-CoA, whereas rat liver microsomes hydrolyzed ibuprofenyl-CoA at a rate similar to whole liver homogenate but had very little epimerization activity. Rat liver cytosol was the poorest at hydrolyzing ibuprofenyl-CoA but had substantial epimerization capability. Whole liver homogenate from human tissue was less efficient at epimerizing but as efficient at hydrolyzing ibuprofenyl-CoA as rat whole liver homogenate. No stereoselectivity of either epimerization or hydrolysis was noted for any of the enzyme preparations studied. This study demonstrates that the inversion of (R)-ibuprofen occurs, at least in part, via the epimerization of the metabolic intermediate, ibuprofenyl-CoA, in both rat and human liver tissues.

Animals↗