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Biomedical subjects

R A Herman

Publications and source records attributed to R A Herman.

7 recordsLinked to original sources
PubMed1990

Effect of aspirin and sulindac on methotrexate clearance.

The pharmacokinetics of low dose methotrexate (MTX) were evaluated in 12 rheumatoid arthritis patients in the presence and absence of steady-state levels of salicylic acid (ASA) and sulindac (SU). Using a Latin square design, patients were given MTX plus ASA (mean 3.4 g/day), MTX plus SU (mean 400 mg/day), or MTX alone. On a background of at least one year of regular MTX therapy, patients received 10 mg/m2 MTX iv (mean 17.8 mg) given after at least 2 weeks of treatment with each of the above regimens. Plasma concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were measured using HPLC. No differences in MTX clearance (Cl) were found comparing MTX alone, MTX + ASA, and MTX + SU. However, if one particular subject that had a very low clearance when receiving MTX alone was excluded, there was a statistically significant decrease in MTX clearance when either ASA or SUL were present. It is also noteworthy that ASA significantly increased the exposure of the subject to 7-OH-MTX and, to a lesser extent, so did sulindac. Since 7-OH-MTX has been shown to be an active metabolite when given for cytotoxic effects at higher doses and because it has been show to be nephrotoxic at doses a thousand-fold greater than used in rheumatoid arthritis, nonsteroidal anti-inflammatory drugs should be used cautiously with MTX until further large scale safety studies are conducted. The data indicate that if a clinically significant interaction were to occur, ASA is more likely than SU to interact with MTX.

Arthritis, Rheumatoid↗
PubMed1989

Pharmacokinetics of low-dose methotrexate in rheumatoid arthritis patients.

The pharmacokinetics and bioavailability of low-dose methotrexate (MTX) (10 mg/m2) were evaluated in 41 subjects who had definite or classical rheumatoid arthritis as defined by the American Rheumatism Association criteria. Subjects received 10 mg/m2 (to the nearest 2.5 mg) of MTX in a single oral dose and a single intravenous (iv) dose one week apart. Serum concentrations for this low-dose regimen were monitored using a radiochemical ligand binding assay. The results indicate the MTX is cleared from the plasma at a rate of 84.6 mL/min/m2. The terminal half-life was approximately 6 h. The volumes of distribution at steady state and for the central compartment were 22.2 and 13.5 L/m2, respectively. The mean residence time in the body, in the systemic circulation, and in the periphery were estimated to be 4.7, 3.0, and 1.7 h, respectively, with a peripheral single-pass mean transit time of 6.0 h and an intrinsic mean residence time in the periphery of 7.9 h. The mean absorption time was 1.2 h and the oral bioavailability was 0.70. The ratio of synovial fluid concentration to serum concentration 4 and 24 h after a dose was found to be approximately 1.0, indicating that at least within that time range serum and synovial fluid concentrations are approximately equal. Because of conflicting results and insufficient data from previous high-dose pharmacokinetic studies, it is difficult to say whether or not low-dose MTX pharmacokinetics differs from those of high-dose MTX.

Administration, Oral↗
PubMed1987

Gold pharmacokinetics in breast milk and serum of a lactating woman.

During 20 weeks of aurothioglucose therapy, gold in a mother's serum and breast milk and her nursing infant's serum and urine were measured. The mother's steady state plasma gold was 4.05 mg/l; it was 0.041 mg/l in breast milk. Only 0.0255 mg gold appeared in the breast milk/24 h. We calculated that only 0.1785 mg gold (0.71% of the weekly dose) would appear in the breast milk over a week. No gold (less than 5 X 10(-7) mg/l) was found in the infant's plasma or urine. It is very unlikely that more than minute amounts of gold are absorbed from the mother's breast milk when breast feeding an infant.

Adult↗