British journal of clinical pharmacology
-
Br J Clin Pharmacol · Sep 1993
Clinical TrialBioavailability and absorption kinetics of nicotine following application of a transdermal system.
1. The absolute bioavailability and absorption kinetics of nicotine were investigated in 13 healthy adult male smokers following single and multiple applications of a nicotine transdermal system (NTS), designed to release nicotine at an approximate rate of 1.5 mg h-1 over 24 h. The absorption of nicotine from the single NTS application was calculated with reference to a simultaneous intravenous infusion (i.v.) of deuterium-labelled nicotine. 2. ⋯ No significant changes were seen in the pharmacokinetics of nicotine between single and multiple applications of NTS. 8. As expected from the higher total plasma nicotine concentrations, the incidence of adverse effects was higher following simultaneous intravenous and transdermal administration of nicotine. The most frequently reported systemic side effects were nervousness and headache: mild itching was the most frequent topical effect.
-
The glucuronidation of morphine was investigated in 10 premature neonates (postnatal age < 24 h at initiation of treatment) following 24 h of therapy (2 h loading infusion, followed by a constant rate infusion). Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured in plasma obtained at 24 h in all babies. Plasma concentrations of M3G and M6G correlated significantly with morphine concentration (P < 0.01 in both cases), and with each other (P < 0.001), suggesting that the capacity for morphine glucuronidation in premature neonates is not saturated at the infusion rates used in this study. ⋯ This probably reflects increase in liver weight with increasing birth weight. Although morphine glucuronidation is deficient in premature neonates, significant concentrations of the respiratory stimulant M3G are achieved rapidly (20% of morphine plasma concentrations at 2 h). At this time, the respiratory depressant M6G could not be detected.
-
The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphine was 20.1 ml min-1 kg-1 in neonates and 23.4 ml min-1 kg-1 in the group as a whole. The M3G/morphine ratio (7.3) was higher than that previously reported for preterm neonates (5.0) but lower than that reported for children (23.9).
-
1. The attitudes and knowledge of doctors in the Northern Region to reporting of adverse drug reactions were assessed using a postal questionnaire to all doctors in two, previously identified, high reporting and two low reporting health districts. Comparisons were made of the attitudes and knowledge within professional groups (GPs, Consultants and Junior Hospital Doctors), and between the amalgamated doctor groups. 2. 1181 of 1600 doctors (74%) responded. ⋯ General Practitioners in low reporting areas stated they wrote more prescriptions (P < 0.02), consultants spent more time in clinical contact (P < 0.01) and junior doctors did both (P < 0.01), all of which suggest different workloads may effect reporting of adverse drug reactions. 5. When given clinical examples, or asked about the CSMs black triangle scheme, all doctor groups performed poorly. 6. The number of reports stated as being sent increased with time from qualification for 10 years, then seemed to plateau.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Br J Clin Pharmacol · Nov 1992
Plasma morphine-3-glucuronide, morphine-6-glucuronide and morphine concentrations in patients receiving long-term epidural morphine.
Plasma morphine concentrations were measured in five cancer patients receiving long-term epidural morphine administration. Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially. Plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations were measured in two patients and plasma M3G concentrations were observed to be much higher than plasma M6G and morphine concentrations. Peak plasma M6G concentrations occurred within 1.0 h of dosing and plasma M6G concentrations then remained higher than plasma morphine concentrations.