Stability and tolerability of high concentrations of intrathecal bupivacaine and opioid mixtures in chronic noncancer pain: an open-label pilot study.

Objective: To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion.

Design: Prospective, open label, pilot cohort study.

Setting: Outpatients at a University medical center.

Transfer of methylamphetamine and amphetamine into breast milk following recreational use of methylamphetamine.

Aims: To investigate the transfer of amphetamines into breast milk following their recreational use and estimate drug exposure for the breastfed infant.

Methods: Two breastfeeding mothers who were occasional recreational users of intravenous amphetamines were studied. A urine sample was collected 4 h after dose, and milk samples were collected over 24 h.

Investigation of target plasma concentration-effect relationships for olanzapine in schizophrenia.

Olanzapine is an atypical antipsychotic effective in the treatment of schizophrenia. The present study has examined the potential use of target concentration monitoring of olanzapine in plasma as a marker of clinical response and an aid in patient management. Fifty-three patients (mean age 32 years; 40 M, 13 F) with a DSM-IVR diagnosis of schizophrenia completed a 6-week trial of oral olanzapine.

Nitazoxanide in treatment of Helicobacter pylori: a clinical and in vitro study.

Nitazoxanide (NTZ) is an antibiotic with microbiological characteristics similar to those of metronidazole but without an apparent problem of resistance. The aim of this study was the prospective evaluation of NTZ given as a single agent in the treatment of Helicobacter pylori infection. Twenty culture-positive patients with dyspepsia who had previously failed at least one course of H.

Optimizing the hydrolysis of codeine and morphine glucuronides in urine.

Quality assurance data show that there is very significant inter-laboratory variation of the quantitation of codeine, especially in patient samples. The authors have examined hydrolysis procedures for codeine glucuronide (C6G) and morphine-3- and -6-glucuronides (M3G, M6G) because these are often present together in urine samples. Comparisons of hydrolysis using two different sources of beta-glucuronidases and various concentrations of hydrochloric acid were made.

Determination of olanzapine in plasma by high-performance liquid chromatography using ultraviolet absorbance detection.

A rapid method for the determination of olanzapine in plasma using high-performance liquid chromatography with ultra violet detection is described. Olanzapine was extracted from plasma with a mixture of hexane/dichloromethane (85:15), and then back extracted into phosphate buffer pH 2.8.

Quantification of naltrexone and 6,beta-naltrexol in plasma and milk using gas chromatography-mass spectrometry. Application to studies in the lactating sheep.

A selective gas chromatography-mass spectrometry method using solid-phase extraction has been developed for the detection and quantification of naltrexone and its metabolite, 6,beta-naltrexol in plasma and milk from humans and sheep at pharmacologically relevant concentrations. Di- or tri-acetyl derivatives were formed and quantified by selected-ion monitoring. Recoveries of naltrexone (30 microg/l) and 6,beta-naltrexol (250 microg/l) from both human plasma and milk were greater than 70%.

The effects of cigarette consumption on the Sternberg visual memory search paradigm.

Aim: To examine the performance of non-smokers (n = 24), light smokers (n = 22, mean 6.5 cigarettes per day) and heavy smokers (n = 19, mean 23 cigarettes per day) on the Sternberg memory search task.

Design: A repeated-measures, counterbalanced design was used with one between-subject factor, status (heavy, light or non-smoker) and two within-subject factors, condition (12 hours abstinence or ad libitum smoking) x time (pre- or post-cigarette).

Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes.

Aims: Gliclazide pharmacokinetics and pharmacodynamics were assessed in 9 Caucasians and 10 Australian Aborigines with uncomplicated type 2 diabetes.

Methods: Subjects were on a stable dose of 80 mg gliclazide twice daily, took 160 mg on the morning of study and had a standard breakfast. No further gliclazide was given over the next 48 h.

Extracorporeal circulatory support in near-fatal flecainide overdose.

Flecainide, a class 1c antiarrhythmic, has a high mortality associated with significant overdose. We report the case of a 20-year-old female who took approximately 4 grams of flecainide and a small amount of paracetamol as an impulsive gesture. Circulatory failure unresponsive to pacing, inotropes and sodium bicarbonate was successfully treated with cardiopulmonary bypass (CPB).

Altered leucocyte trafficking and suppressed tumour necrosis factor alpha release from peripheral blood monocytes after intra-articular glucocorticoid treatment.

Objectives: A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects.

Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk.

Aims: To characterise the transfer of venlafaxine (V) and its O-desmethyl metabolite (ODV) into human milk by measuring milk/plasma (M/P) ratio, and to estimate the likely dose received by a breast-fed infant.

Methods: Milk and plasma samples were collected from three lactating women who were taking venlafaxine for depression, and were at steady-state. In two of the patients, venous blood and milk samples were collected 0, 1, 2, 3, 4, 6, 8 and 12 h post dose, while in the third patient a single pair of blood and milk samples was obtained 0.

Distribution and excretion of sertraline and N-desmethylsertraline in human milk.

Aims: To characterise milk/plasma (M/P) ratio and infant exposure, for sertraline and N-desmethylsertraline, in breast-feeding women taking sertraline for the treatment of depression.

Methods: Eight women (mean age 28 years) taking sertraline (1.05 mg kg(-1) day(-1)) and their infants (mean age 5.

A comparison of high-performance liquid chromatography and fluorescence polarization immunoassay for therapeutic drug monitoring of tricyclic antidepressants.

Although the manufacturer of the polyclonal fluorescence polarization immunoassay (FPIA) for tricyclic antidepressants (TCA) only recommends its use in the diagnosis of overdose, the assay is nevertheless widely used in therapeutic drug monitoring. Using plasma samples from 337 patients taking one of eight different tricyclic antidepressants, the authors investigated the performance of the TDx assay procedure for eight different TCAs by comparison to specific high-performance liquid chromatography (HPLC) assay methods. The regression correlation between the TDx assay value and that for active tricyclic measured by HPLC was poor (r2 < 0.

Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme.

Aims: Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug.

Methods: Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20-80 mg (0.

Population pharmacokinetics of felbamate in children.

Information about the pharmacokinetics of felbamate in children is limited. Even though it is claimed that monitoring of felbamate concentrations is unnecessary, many neurologists have requested therapeutic drug monitoring (TDM) for various reasons. This study used the NONMEM program to describe the pharmacokinetics and the influence of other anticonvulsants on the pharmacokinetics of felbamate.

Distribution and excretion of sumatriptan in human milk.

1. The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg.

Antidepressant toxicity and the need for identification and concentration monitoring in overdose.

Antidepressant drugs are among the most commonly encountered causes of self-poisoning. These drugs include tricyclics, tetracyclics, bicyclics and monocyclics, as well as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Of these, the tricyclic antidepressants (TCAs) are generally more toxic in overdose, with major toxicity usually manifesting within the first 6 hours after overdose.

The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects.

1. The mechanism of the interaction between ciprofloxacin and theophylline was investigated in nine healthy subjects. 2.

Disposition of lupanine and 13-hydroxylupanine in man.

1. The in vivo disposition of lupanine and 13-hydroxylupanine was studied in subjects identified as poor metabolizers (PM, n = 4) and extensive metabolizers (EM, n = 7) phenotypes for cytochrome P4502D6 (CYP2D6). 2.

Patterns of drug use by participants in the Western Australian methadone program, 1984-1991.

Objectives: To establish the extent to which participants in the WA methadone treatment program used opiates, cannabinoids, benzodiazepines, cocaine and amphetamines, and to define the pattern of such use over time. In addition, the relationships between methadone daily dose and the use of the various drug groups was examined.

Design: A retrospective analysis of data from 1678 samples from urinalysis screening over 13 separate surveys between 1984 and 1991.

Excretion of lignocaine and its metabolite monoethylglycinexylidide in breast milk following its use in a dental procedure. A case report.

The excretion of lignocaine in breast milk has been documented in a 34-year-old woman following the injection of 20 mg lignocaine for a dental alloy restoration in the right upper quadrant. Lignocaine and its primary metabolite monoethylglycinexylidide in milk and plasma were quantified by high-performance liquid chromatography. The concentration of lignocaine in milk ranged from 44-66 micrograms l-1 while that for monoethylglycinexylidide ranged from 35-41 micrograms l-1.

Comparison of cyclosporine measurement in whole blood by high-performance liquid chromatography, monoclonal fluorescence polarization immunoassay, and monoclonal enzyme-multiplied immunoassay.

Monitoring of cyclosporine concentrations in whole blood is used routinely as a guide to adjusting dose so as to achieve optimal therapeutic benefit with minimal adverse effects. In the present study, we have compared a specific high-performance liquid chromatography (HPLC) assay with a fluorescence polarization immunoassay (TDx) and an enzyme-multiplied immunoassay (Emit). Both Emit and TDx assays employ a monoclonal antibody to cyclosporin A and therefore have the potential for a high degree of specificity.

The excretion of dothiepin and its primary metabolites in breast milk.

1. The excretion of dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide into breast milk was studied in eight women. Exposure to drug was measured in five of their infants, and possible drug-related effects were assessed in all eight infants.