Administering codeine to breast-feeding mothers had been considered safe until the recent death of a breast-fed neonate whose mother had been prescribed codeine. We investigated the risk of opioid poisoning to breast-fed neonates using coupled physiologically based pharmacokinetic models for the mother and child. Neonatal morphine plasma concentrations were simulated for various combinations of cytochrome P450 2D6 (CYP2D6) genotype and morphine clearance, assuming typical breast-feeding schedules and maternal codeine doses of

The pharmacokinetics of Nimodipine were studied in healthy volunteers and in patients with subarachnoid hemorrhage (SAH) following cerebral aneurysm rupture. Nimodipine was absorbed rapidly. After an oral dose of 120 mg an average maximal plasma concentration 106 micrograms/l was recorded 45 to 60 minutes later. During a 7-day oral therapy with 40 mg t.i.d. no accumulation or change in the absorption or elimination kinetics occurred. After i.v. administration a biphasic elimination with half lives of 7 min and 1 hour was observed. In patients with subarachnoid hemorrhage receiving a continuous infusion of 2 mg/hour the mean nimodipine plasma concentrations ranged between 36 and 72 micrograms/l. Subsequent oral dose of 60 mg q.i.d. to the same patients resulted in concentrations ranging between 17 to 42 micrograms/l on the average one hour after the dosage. Mean cerebrospinal fluid (CSF) levels amounted to 0.3 +/- 0.2 microgram/l in patients whose mean plasma concentrations were 76.9 +/- 34.0 micrograms/l.

The absence of an absorption window in the intestinal tract suggests that nifedipine is well suited for use in controlled-release formulations.

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