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Biomedical subjects

A Lopez-Anaya

Publications and source records attributed to A Lopez-Anaya.

6 recordsLinked to original sources

Pharmacokinetics of zidovudine (azidothymidine). III. Effect of pregnancy.

Administration of zidovudine (ZDV or azidothymidine) to pregnant women with HIV infection may be of benefit to both the mother and her unborn child. Since pregnancy can have a substantial effect on the pharmacokinetics of a drug, the effect of pregnancy on the pharmacokinetics of ZDV (10 mg/kg, i.v. bolus) was studied in the macaque (Macaca nemestrina). The plasma clearance, steady-state volume of distribution, and terminal half-life of ZDV were found not to be significantly affected by pregnancy. Based on these findings, we predict that the pharmacokinetics of ZDV in women will not be affected by pregnancy. If this prediction is found to be correct, the dose of ZDV need not be adjusted when the drug is administered to pregnant women.

Animals

Simple and effective procedure for complete urine collection from infant macaques (Macaca nemestrina).

A diaper method, used in pediatric medicine, has been adapted and validated for total urine collection from infant macaques (Macaca nemestrina). The device consists of cellulose sponges and polyethylene sheets. The method proposed is non-invasive, simple, and does not significantly hinder the movement of the infant. The method should be useful when one is conducting pharmacokinetic studies in which total urine collection is required.

Animals

Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate.

The pharmacokinetics of zidovudine (ZDV or azidothymidine) were investigated in newborn macaques (Macaca nemestrina) at various ages ranging from less than 1 week to 4 months. The mean ZDV total plasma clearance, renal clearance, and the metabolic clearance of ZDV to the glucuronide (ZDVG) were significantly (p less than 0.05) smaller during the first week of life (6.15 +/- 1.03, 4.25 +/- 0.36, and 1.19 +/- 0.67 ml/min/kg, respectively) than the corresponding estimates at the age of 4 months (19.62 +/- 3.5, 8.28 +/- 1.90, and 8.28 +/- 2.24 ml/min/kg, respectively). The mean estimates of these parameters at 4 months were close to those found in adult macaques (23.55 +/- 1.48, 10.05 +/- 0.75, and 10.5 +/- 1.9 ml/min/kg, respectively), indicating that these clearance pathways develop rapidly, within 4 months of birth. If similar results are obtained in human neonates, therapeutic drug monitoring should be instituted when administering ZDV to this population so that the dose of ZDV may be adjusted to correspond with age-related changes in total plasma clearance of ZDV.

Aging

Pharmacokinetics of zidovudine (azidothymidine). I. Transplacental transfer.

Administration of zidovudine (ZDV) to pregnant women with human immunodeficiency virus infection may be of benefit to both the mother and the unborn child. Before testing this hypothesis, however, it is necessary to determine the transplacental transfer, fetal toxicity, and fetal accumulation of ZDV (if any) in a representative animal model. Therefore, the transplacental transfer and the fetal accumulation of ZDV were determined at steady state in near-term pregnant macaques (Macaca nemestrina). ZDV was administered to five dams at a rate predicted to produce a steady-state plasma concentration of about 1 microgram/ml. When steady state was predicted to have been achieved, a cesarean section was performed on each dam. At this time, blood samples from the dam (peripheral vein) and the fetus (umbilical vein) were obtained simultaneously. The plasma concentration of ZDV and its major metabolite, zidovudine glucuronide (ZDVG), were determined by a specific high-performance liquid chromatography (HPLC) method. The ratio of steady-state plasma concentration (Crss) of ZDV in the fetus (Cssf) to that in the dam (Cssd) (Crss = Cssf/Cssd) was found to be close to unity (0.826 +/- 0.067). Similar results were obtained for the ratio of steady-state unbound ZDV plasma concentration (0.852 +/- 0.083). We conclude that ZDV readily crosses the placenta, probably by passive diffusion, and that ZDV does not accumulate in the fetus when administered to near-term pregnant macaques.

Amniotic Fluid

Quantification of riboflavin, riboflavin 5'-phosphate and flavin adenine dinucleotide in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method with fluorimetric detection for the quantification of riboflavin (RB), riboflavin 5'-phosphate (FMN), and flavin adenine dinucleotide (FAD) in plasma, whole blood, and urine is described. Under isocratic conditions with a reversed-phase column, the compounds are completely resolved and eluted within 9 min. Plasma proteins are precipitated with acetonitrile followed by shaking the aqueous phase with chloroform. Urine samples are diluted and injected directly. The reproducibility of this method for the quantification of RB in plasma has a between-day coefficient of variation of 6%. The application of this method is illustrated by analyzing plasma and urine samples from a human subject who received an intravenous dose of FMN equivalent to 25 mg of RB.

Adult

Ascorbic and dehydroascorbic acids simultaneously quantified in biological fluids by liquid chromatography with fluorescence detection, and comparison with a colorimetric assay.

We describe a "high-performance" liquid-chromatographic method for separating and quantifying ascorbic acid (AA) and dehydroascorbic acid (DHA) in plasma and urine. We used a reversed-phase C18 column with an ion-pair reagent and detected the analytes by post-column reaction with 4,5-dimethyl-o-phenylenediamine to form a fluorescent derivative (measured at excitation and emission wavelengths of 365 and 440 nm, respectively). Isoascorbic acid (IA) is the internal standard. Retention times for DHA, AA, and IA are 5.6, 15.5, and 19.9 min, respectively. Between-day CVs for AA in plasma in concentrations of 8 and 20 mg/L were 9% and 7%, respectively. The limit of detection is 10 and 4 ng for AA and DHA, respectively. Results by the present method and the methoxyaniline colorimetric method for AA are comparably accurate.

Ascorbic Acid