Salicylate kinetics in old age.

Salicylate kinetics were determined in 28 subjects 25 to 92 years old who received single, oral doses of sodium salicylate (1 gm/1.73 m2). The serum AUCinfinity of total salicylate did not correlate with age. There was a weak positive correlation between the AUCinfinity of free (unbound) drug and age, but there was no apparent difference between the AUCinfinity values of the 15 women and 13 men. Seven of the 16 subjects greater than 70 years of age cleared salicylate at about the same rate as the younger subjects. A comparison of these seven subjects with the nine greater than 70 years old who were slow eliminators of salicylate revealed that the latter group consisted of more bedridden patients and that these patients had somewhat lower serum albumin concentrations, but they did not differ from the more rapid eliminators with respect to serum creatinine or urea nitrogen levels, SGOT, average age, female/male ratio, and average body weight. The serum protein binding of salicylate decreased with increasing age, apparently due mainly to decreasing serum albumin concentrations.

Pharmacokinetic monitoring of salicylate therapy in children with juvenile rheumatoid arthritis.

Free and total (sum of free and protein bound) salicylate concentrations in serum were determined in 17 children (age: 4-17 years) with definite juvenile rheumatoid arthritis. These measurements were carried out immediately before and 2, 4, and 8 hours after the morning dose during a strict 8 hourly aspirin treatment regimen (regular tablets) started 5 days earlier. The ratio of the 0 to 8 hour total salicylate concentrations was 0.95 +/- 0.10 (mean +/- SD), indicating that steady state had been attained. The ratio of the maximum to minimum concentrations during the dosing interval ranged from 1.05 to 2.26 and decreased with increasing average concentration. The concentration ratio was less than 1.3 at average salicylate concentrations above 20 mg/100 ml. It is concluded that the timing of a blood sample is not critical for monitoring steady state serum salicylate concentrations in the usual therapeutic range if the dosing interval is 8 hours or less. Free salicylate concentrations increased more than proportionately with increasing total concentrations due to the concentration dependent protein binding of the drug in serum.

Effect of renal transplantation on protein binding of drugs in serum of donor and recipient.

Blood samples were obtained periodically before and for about 3 mo after renal transplantation from a donor (mother) and a recipient (9-yr-old son with bilateral nephrectomy) for determination of serum protein binding of salicylate and sulfisoxazole. Ten days after the transplant, the recipient had an acute rejection episode which was treated successfully. The free fraction values of the drugs in serum of the recipient was considerably above normal before transplantation, decreased to normal within 2 days after transplantation, increased again several days before the rejection episode and remained elevated for about 50 days, and then returned to normal. Serum protein binding of the drugs in the serum of the donor was decreased for only a few days after transplantation and then returned to normal.

Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium.

The post-distributive neonatal:maternal plasma salicylate concentration ratio following salicylate administration to the mother before delivery is appreciably higher than unity. The protein binding of salicylate and the albumin concentration in one such plasma pair were considerably higher in the neonatal than in the maternal plasma. Equilibrium dialysis of neonatal plasma or serum from 6 newborn infants against that of their mothers produced a neonatal: maternal salicylate concentration ratio above unity in all cases even if the albumin concentration in the neonatal serum did not exceed that in the maternal serum. However, there was a strong correlation between the neonatal:maternal concentration ratios of salicylate and albumin. These observations demonstrate that conclusions concerning the distribution of a drug across the placenta in relation to its plasma protein binding characteristics must be based on the results of binding studies with plasma or serum from neonates and their mothers, and not from other adult subjects.

Fetal acquisition and neonatal elimination of a large amount of salicylate. Study of a neonate whose mother regularly took therapeutic doses of aspirin during pregnancy.

The purpose of this study was to determine the amount of salicylate acquired by a newborn infant from a mother who took 6.5 gm of aspirin a day during her entire pregnancy, and to characterize the kinetics of salicylate elimination by the infant. This healthy female infant was born with a salicylic acid concentration of 25 mg/100 ml plasma and 75 mg/kg body weight. The drug was eliminated during the first 5 days of life, primarily in the form of salicyluric acid. Salicylate elimination was relatively slower than in normal adults, but more rapid than in newborn infants of mothers who had taken only one small dose of aspirin shortly before delivery. The apparent in vivo KM and Vmax for salicylurate formation, on a body weight basis, were at the adult level. The slower elimination of salicylate (relative to adults) by the infant was due to immaturity of the glucuronidation and renal excretory pathways.