PHARMACOKINETICS AND BIOAVAILABILITY OF METOCLOPRAMIDE NASAL SPRAY VERSUS METOCLOPRAMIDE INTRAVENOUS IN HEALTHY-VOLUNTEERS AND CANCER-PATIENTS

The kinetics and bioavailability of a new formulation of metoclopramid e (CAS 364-62-5) nasal spray (MTC NS) were assessed in two separate st udies versus the same drug administered intravenously (MTC IV) accordi ng to a balanced-block design where each study subject served as his o wn controL The first study involved 10 healthy subjects, each receivin g metoclopramide NS 20 mg (one 10-mg puff per nostril) and metoclopram ide IV 20 mg on two trial days separated by a 7-day, washout period On both occasions, blood samples were obtained at time 0 and at 20, 40, 60, 120, 150, 210, 280 and 360 min of dosing. Metoclopramide concentra tions were assayed in plasma by HPLC. The second study involved 10 pat ients of oncologic domain, scheduled to receive mildly emetic chemothe rapy regimes. The experimental design was similar to the one above exc ept that blood was sampled at 0, 20, 40 and 60 min and again at 2, 3, 4, 6, and 8 h of dosing. All healthy subjects completed the trial with out experiencing any adverse or untoward events; in the group of cance r patients, one subject dropped out after the nose spray treatment whe n he was removed to another department. This patient was replaced by a nother, and included in final data analysis only for the segment of tr eatment actually received. Metoclopramide kinetics after intravenous d osing were in good agreement with known data for the active substance, with no meaningful differences between healthy subjects and cancer pa tients. With MTC NS administration there was only a slight but signifi cant difference of C(max), being lower in the cancer patient group (p < 005). Said difference appears clinically irrelevant, since T(max) an d AUC values compared closely in the two groups. Absolute bioavailabil ity (MTC NS vs MTC IV) was 69% in the healthy subjects and 73% in the patient group. T(max) was between 2 and 3 after dosing; plasma elimina tion rate constants was in keeping with established metoclopramide dat a.