The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · Dec 1996
A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers.
A pharmacokinetic study was undertaken to compare the pharmacokinetics of morphine after an intravenous dose with the pharmacokinetics after a sublingual dose administered from an aerosol. Plasma levels of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in five normal volunteers after morphine administration by the intravenous route and from a novel sublingual pressurized aerosol formulation. The mean (+/- s.d.) bioavailability of the sublingual aerosol morphine was 19.7 +/- 6.7%. ⋯ When compared with published data for oral administration the results demonstrate that the sublingual aerosol morphine might provide an alternative to conventional methods of morphine delivery, and has similar pharmacokinetics to a sublingual morphine tablet. It has no particular pharmacokinetic advantages over oral morphine, except a potential for a faster onset of analgesia. Bioavailability, maximum plasma concentration, Cpmax, and the time at which the maximum plasma concentration is reached, Tmax, are equivalent to those for orally administered morphine.
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J. Pharm. Pharmacol. · Jan 1996
Review Comparative StudyBioequivalence and generic prescribing: an industrial view.
The whole concept of bioequivalence is based upon the existence of a clear relationship between drug concentration and clinical effect. To date there are insufficient data available in the form of publications to support this concept. ⋯ Upon expiry of the patent, regulators could provide estimates of the inter- and intra-subject variability in the pharmacokinetics of a drug in volunteers and patients, assessment of therapeutic windows for drugs and drug classes and their impact on bioequivalence acceptance criteria. Current regulatory guidelines refer to rate and extent of absorption BUT there is no rate parameter which allows products to be compared for both pharmaceutical quality and safety and efficacy.
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J. Pharm. Pharmacol. · Dec 1995
Comparative StudyEffects of clonidine pretreatment on the local anaesthetic activity of bupivacaine in mice.
This study was designed to document possible changes in bupivacaine local anaesthetic activity in mice after a single injection of clonidine (0.1 or 1 mgkg-1, i.p.). The local anaesthetic activity was evaluated during 60 min, according to a previously reported technique, using sciatic nerve blockade by injection of bupivacaine in the area of the sciatic nerve. ⋯ The maximal effect (Emax) was significantly lower for the pretreated group (1.15 +/- 0.13 units, 0.1 mgkg-1; 1.35 +/- 0.09 units, 1 mgkg-1) compared with the control group (1.72 +/- 0.13, P = 0.01). Our data indicate a significant decrease in the duration of anaesthetic activity of bupivacaine in clonidine-pretreated mice.
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J. Pharm. Pharmacol. · Jun 1994
Evaluation of free radical production in an ischaemia-reperfusion model in the rabbit using a tourniquet.
Use of a tourniquet on a limb to stem blood flow is frequent in surgery. However, this results in an ischaemia-reperfusion effect that causes damage through the production of free radicals. ⋯ Plasma lipoperoxides were measured by high-performance liquid chromatography using the malondialdehyde assay method. We found significant (P < 0.01) production of free radicals 1 min after release of the tourniquet compared with controls; no variation in levels of free radicals was observed during the ischaemia phase.
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The poor solubility of steroid anaesthetics in water has been a serious drawback in the development of clinically acceptable intravenous formulations. The use of Cremophor EL to solubilize steroids such as alphaxalone led to unacceptable hypersensitivity reactions and consequent withdrawal of this anaesthetic. In principle, liposomes can act as a safe solvent for the intravenous administration of alphaxalone. ⋯ The rate of efflux of this anaesthetic from a range of liposomes was measured in serum. The highest rate (85% after 30 min) was observed with an equimolar egg phosphatidylcholine:cholesterol stable plurilamellar vesicle preparation. From these studies it can be concluded that liposomes offer a suitable alternative for intravenous delivery of steroidal anaesthetics.