Preventing pain during injection of propofol: effects of a new emulsion with lidocaine addition.

BACKGROUND AND OBJECTIVE: Previous studies found that lidocaine addition to propofol long-chain triglyceride was associated with a lower incidence of injection pain than medium-chain triglyceride/long-chain triglyceride formulation, but the incidence was still high (31-40%). Our study investigated whether the incidence of injection pain could be further reduced by the addition of lidocaine (10 mg, 20:1) to propofol medium-chain triglyceride/long-chain triglyceride. METHODS: In a randomized double-blind controlled trial 464 patients scheduled to undergo regional anaesthesia were assigned to receive one of the following four options: propofol medium-chain triglyceride/long-chain triglyceride + lidocaine, propofol long-chain triglyceride + lidocaine, propofol medium-chain triglyceride/long-chain triglyceride or propofol long-chain triglyceride. Propofol was injected to reach grade 3 of the Observer's Assessment of Alertness/Sedation scale. RESULTS: Incidence of injection pain was 18% in the propofol medium-chain triglyceride/long-chain triglyceride + lidocaine group, 31% in the propofol long-chain triglyceride + lidocaine group, 47% in the propofol medium-chain triglyceride/long-chain triglyceride group and 60% in the long-chain triglyceride group. Propofol medium-chain triglyceride/long-chain triglyceride + lidocaine was associated with a statistically significant reduced incidence of injection pain compared with propofol long-chain triglyceride +lidocaine (P =0.0249, number needed to treat =7.7). CONCLUSIONS: Premixing propofol medium-chain triglyceride/long-chain triglyceride with lidocaine is one of the most effective measures currently available to reduce the incidence of injection pain in sedated patients during regional anaesthesia.

Studies on the pharmacokinetics of chlorambucil and prednimustine in patients using a new high-performance liquid chromatographic assay.

Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies.

A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma.

A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2-chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy.

[Investigations in Bioavailability of resinates as peroral retard drug dosage forms. Part 1: Pharmaceutical availability of dihydrocodein-resinates (author's transl)]. / Untersuchungen zur Bioverfügbarkeit von Resinaten als perorale Depot-Arzneimittel. 1. Mitteilung: Pharmazeutische Verfügbarkeit von Dihydrocodein-Resinaten.

The dissolution rate constants of dihydrocodein in two retard drug dosage forms based on synthetic ion exchange resin were determined with four dissolution methods. The usage of the flow cell, rotationsdisk method and half-change method with a new dissolution model gave comparable results. Using the paddle apparatus the dissolution is very quick. There is only a small influence on the dissolution rate by the pH. A higher ionic strength of the dissolution medium increases the dissolution rate.