Peter R. Lewy

Pharmacokinetic studies of prednisolone in children: Plasma levels, half-life values, and correlation with physiologic assays for growth and immunity**

Plasma prednisolone levels have been measured hourly in children receiving a single dose of oral prednisone. Peak prednisolone levels occurred one to two hours after ingestion; half-life studies gave a mean value of 132 minutes in most children. Some children had marked variability in absorption and metabolism of prednisone. Somatomedin activity and cell-mediated immunity were inhibited by plasma prednisolone values which were achieved by single doses of prednisone of 0.5 mg/kg or higher. Monitoring prednisolone levels may be of value in identifying those children who accumulate excessively high levels on moderate dosage regimens.

Familial occurrence of nonobstructive, noninfectious vesicoureteral reflux with renal scarring

A family is described in which gross vesicoureteral reflux and renal scarring are present in the father and three sons, none with a history of urinary tract infection. Vesicoureteral reflux alone is present in an infant daughter. Father-to-son transmission of vesicoureteral reflux has not been previously reported. Autosomal dominant inheritance of the trait is suggested. The renal scarring noted in these patients may reflect generalized maldevelopment of affected renal units. The increasing recognition of vesicoureteral reflux as a familial trait suggests the need for evaluation of families in which vesicoureteral reflux is found in more than one member.

Nephrotic syndrome in association with renal vein thrombosis in infancy

A 10-week-old girl with nephrotic syndrome was found at autopsy to have bilateral renal vein thrombosis. The association of RVT with nephrotic syndrome in infancy is extremely uncommon, except in congenital (familial) nephrosis. RVT with nephrosis occurring in adults with membranous nephropathy is a well-recognized entity. Whether the thrombosis or the nephrosis is the primary disorder remains controversial. The findings in the present patient suggest that the RVT may be the initiating event in some patients. This may represent a reversible cause of infantile nephrosis.

Acute transient renin-mediated hypertension in children following urinary diversion*

Abstract Six children with unexplained, acute, transient postoperative renin-mediated hypertension were seen in a seven-month period. All patients had severe hydronephrosis and mild impairment of renal function for which permanent urinary diversion was performed. No obvious changes in electrolyte values, circulation, blood volume, or increased urinary obstruction were noted. Antihypertensive therapy was required in 5 patients. Normalization of blood pressure occurred within six weeks or less in all patients.

PREDNISOLONE PHARMACOKINETICS IN CHILDREN

Clinical observations suggest that some children with chronic diseases respond variably to corticosteroid treatment. 33 children have been studied for bio-availability and metabolism of orally administered prednisone. Physiological doses have been investigated in 5 children with congenital virilizing adrenal hyperplasia; pharmacological doses in 8 patients with dermatomyositis (DMS), 7 with systemic lupus erythematosus (SLE), 9 with childhood nephrosis (N), 2 with regional enteritis, 1 asthmatic and 1 renal transplant patient. Plasma prednisolone values have been determined by a specific radioimnunoassay developed in our lab. Bio-availability was calculated from peak plasma prednisolone levels attained; plasma½ -life values from % disappearance from peak values over hourly time intervals. Results indicate: (1) a regression line may be calculated for dose vs peak levels but there is wide variation among patients in bio-availability; (2) ½-life in children differs from adults (mean 125 minutes vs adult 205 minutes); (3) some children with N and DMS have impaired bio-availability but normal ½-life values; (4) a few children with severe disease (SLE, DMS) have markedly prolonged ½-life values. These studies support observations of clinical variability of drug effects when prednisone is utilized in pharmacolgical doses. Knowledge of bio-availability and metabolism may allow more precise and rational therapeutic programs.