Pharmacokinetic assessment of an oral enalapril suspension for use in children

Abstract

The angiotensin-converting enzyme (ACE) inhibitor enalapril is commonly used to treat pediatric hypertension. Because some children are unable to swallow tablets or require doses less than the lowest available enalapril tablet, an enalapril suspension was developed. This study examined the relative bioavailability of enalapril suspension (10 mg) (S) compared with 10-mg marketed VASOTEC tablets (T) in 16 healthy adult subjects. The geometric mean ratio (S/T) estimate of urinary recovery of free enalaprilat, the active moiety, was 0.92 (90% confidence interval (CI): 0.80, 1.07). Urinary recovery data indicate that approximately 50% of the dose was absorbed (50% recovered in urine as enalapril plus enalaprilat) with about 30% of the dose recovered as free enalaprilat for both S and T. The geometric mean ratios (S/T) of serum AUC and C(max) were 1.01 (90% CI: 0.90, 1.13) and 0.98 (90% CI: 0.83, 1.16), respectively. Suspension T(max) was slightly shorter (0.5 h) than that for tablet, but this difference is not clinically significant. Both formulations were well tolerated and there were no clinically significant adverse experiences. We conclude that the bioavailability of enalapril oral suspension 10-mg is similar to that of VASOTEC 10-mg tablet. Instructions for compounding enalapril are provided.

Effects of antihypertensive drugs on blood pressure and proteinuria in childhood

“…We excluded reports which deal with the pharmacokinetics of antihypertensive agents [2][3][4][5][6][7][8][9], with the management of hypertensive emergency, neonatal hypertension or heart failure, or with the management of minimal range albuminuria in diabetes mellitus [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24], or include fewer than 10 individuals [25][26][27][28][29][30][31][32][33][34][35][36]. Trials examining antihypertensive drugs for periods less than 4 weeks [37][38][39], reports not describing the outcome of interest [40][41][42][43][44][45][46][47][48] or describing the effect of a substance added to another, both with the same mechanism of action …”

Bioavailability of a pediatric amlodipine suspension

“…Similar to our study, a recent study on a suspension of enalapril for children used adult volunteers [12]. Ideally, this study should have used children as research subjects, as the pediatric suspension is aimed at them.…”

“…Ethically, however, it is very difficult to perform a meaningful bioavailability study in children due to the numerous blood samples needed. They concluded that the slow transfer of drug from the gut to the venous circulation is a physiochemical property of amlodipine, and not a consequence of delayed or slow dissolution from the capsule formulation [12]. Very few studies measured bioavailability in children by repeating intravenous and oral doses and no study has compared bioavailability in children with adults.…”

An integrated Physiology-Based Model for the Interaction of RAA System Biomarkers With Drugs

“…47,48 This intrarenal conversion was implemented by inclusion of an additional conversion clearance within the intracellular compartment of the kidneys. Data on urinary excretion of enalapril, enalaprilat, and their combination were used to estimate clearance parameters, 49 with a resulting specific intrarenal conversion clearance of 1.95E+05 L$min 21 $kg 21 organ, and an excretion clearance of 0.36 for intrarenal enalaprilat and 3.45 L$min 21 $kg 21 organ for enalapril.…”