NICARDIPINE Solution for injection Ref.[8184] Active ingredients: Nicardipine

Absorption

Following intravenous administration, Nicardipine is rapidly absorbed with studies showing the time to onset ranging between 5-15 minutes. Peak plasma levels can reach 184 ng/ml and steady state plasma concentrations of 157 ng/ml achieved within 24-48 hours of continuous infusion.

Distribution

Nicardipine is highly protein bound in human plasma over a wide concentration range.

Metabolism

Nicardipine is metabolized by cytochrome P450 3A4. Studies involving either a single dose, or administration 3 times daily for 3 days, have shown that less than 0.03% of unchanged nicardipine is recovered in the urine in humans after oral or intravenous administration. The most abundant metabolite in human urine is the glucuronide of the hydroxy form, which is formed by the oxidative cleaving of the N-methylbenzyl moiety and the oxidation of the pyridine ring.

Elimination

After coadministration of a radioactive intravenous dose of nicardipine with an oral 30 mg dose given every 8 hours, 49% of the radioactivity was recovered in the urine and 43% in the faeces within 96 hours. None of the dose was recovered as unchanged nicardipine in the urine. The elimination profile of the drug following an intravenous dose consists of three phases, with corresponding half-life: distribution 6.4 min, elimination 1.5 hours, terminal elimination 7.9 hours. Studies have shown clinical offset of action to be approximately 15 minutes.

Renal impairment

The pharmacokinetics of intravenously administered nicardipine was studied in subjects with severe renal dysfunction requiring hemodialysis (creatinine clearance <10 ml/min), mild/moderate renal dysfunction (creatinine clearance 10-50 ml/min) and normal renal function (creatinine clearance >50 ml/min). At steady state, C_max and AUC were significantly higher and clearance significantly lower in subjects with mild/moderate renal function compared to subjects with normal renal function. There were no significant differences in the principal pharmacokinetic parameters between severe renal dysfunction and normal renal dysfunction (see section 4.4).

Nicardipine has been shown to pass into the milk of lactating animals. It has been reported in animal experiments that the drug is excreted into breast milk. In animal experiments where this drug was administered at a high dose during the terminal stage of pregnancy, an increase in fetal deaths, delivery disturbances, decrease in the body weight of offsprings, and suppression of post-natal body weight gain were reported. However, toxicity to reproduction has not been reported.