Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with fosamprenavir-ritonavir in opioid-dependent subjects.

Study Objective: To compare steady-state pharmacokinetics and pharmacodynamics of methadone enantiomers when coadministered with fosamprenavir 700 mg-ritonavir 100 mg twice/day.

Design: Open-label, single-sequence, two-period crossover, drug-interaction study.

Setting: Two university-affiliated research centers.

Quantitative analysis of the P-glycoprotein inhibitor Elacridar (GF120918) in human and dog plasma using liquid chromatography with tandem mass spectrometric detection.

A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the determination of the P-glycoprotein and breast cancer resistance protein inhibitor Elacridar in human and dog plasma is described. The internal standard was stable isotopically labelled Elacridar. Sample pretreatment involved liquid-liquid extraction with tert-butyl methyl ether.

Determination of the cephalosporin antibiotic cephradine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A simple and sensitive high-performance liquid chromatographic method, for the determination of cephradine in human plasma samples has been developed and validated. Cephradine and cephaloridine (internal standard) were extracted from human plasma by perchloric acid protein precipitation followed by centrifugation. Aliquots of the extracts were analysed by reversed-phase high-performance liquid chromatography (HPLC) utilising a polymeric reversed-phase PLRP-S column, followed by ultraviolet detection at 260 nm.

Rapid determination of the anti-cancer drug chlorambucil (Leukeran) and its phenyl acetic acid mustard metabolite in human serum and plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry.

A bioanalytical method for the determination of the anticancer drug chlorambucil (Leukeran) and its phenyl acetic acid mustard metabolite in human serum and plasma is described. Automated solid-phase extraction of the analytes is carried out with C18 sorbent packed in a 96 well format microtitre plate using a robotic sample processor. The extracts are analysed by isocratic reversed-phase liquid chromatography using pneumatically and thermally assisted electrospray ionisation (TurboIonspray) with selected reaction monitoring.

The electroanalysis of mannitol, xylose and lactulose at copper electrodes: voltammetric studies and bioanalysis in human urine by means of HPLC with electrochemical detection.

The electrochemical behavior of mannitol, xylose and lactulose has been investigated at a copper working electrode. A sensitive, accurate and precise method employing HPLC with electrochemical detection in the d.c.

Validation of chromatographic methods in biomedical analysis. Viewpoint and discussion.

Bioanalytical method validation is the process used to establish that a quantitative analytical method is suitable for biomedical applications. Reassurances as to the quality of the method and its reliability come from adopting a minimum series of validation experiments and obtaining satisfactory results. Consistent evaluation of the key analytical parameters: recovery, response function, sensitivity, precision, accuracy, selectivity and stability, is discussed with a view to improving scientific standards in manuscripts submitted for publication.

Peptide histidine valine: its haemodynamic actions and pharmacokinetics in man differ from those of vasoactive intestinal peptide and peptide histidine methionine.

1. The effects of intravenous and intra-arterial infusion of the peptides derived from prepro-vasoactive intestinal peptide, vasoactive intestinal peptide, peptide histidine methionine and peptide histidine valine, were examined in six healthy volunteers. 2.

DOPA decarboxylase inhibition does not influence the diuretic and natriuretic response to exogenous alpha-atrial natriuretic peptide in man.

The role of dopamine synthesis in the renal actions of human alpha-atrial natriuretic peptide (alpha ANP) was investigated in six dehydrated volunteers using the DOPA decarboxylase inhibitor carbidopa. Each subject received oral placebo or carbidopa (100 mg) followed by an infusion of alpha ANP 10 pmol.kg-1.

Differential effect of high-dose naloxone on the plasma adrenaline response to the cold-pressor test.

1. Although the opiate antagonist naloxone has been shown to affect sympathoadrenomedullary function in some studies, this has not been a uniform finding in all investigations, using different doses of naloxone. We have therefore investigated the actions of saline placebo and increasing bolus doses of intravenous naloxone (25, 100 and 250 micrograms/kg) on the plasma noradrenaline, adrenaline, adrenocorticotrophin (ACTH) and cortisol responses to a cold-pressor test in six males and two females in a double-blind randomized study.

Leukotriene E4 release in cold urticaria.

Cold urticaria is a rare condition characterized by abnormal wealing following exposure to cold. It has been suggested that lipid-derived mediators may be involved in the pathogenesis of this condition. We have investigated whether the inflammatory reaction in cold urticaria is associated with the release of cysteinyl-leukotrienes.

Development of a solid-phase extraction technique for alpha-human atrial natriuretic peptide in human plasma.

A reliable extraction method was developed for alpha-human atrial natriuretic peptide (alpha-hANP) using Bond Elut C8 columns in tandem. This involved activation of the columns using methanol followed by a water wash to remove the excess methanol. Plasma (1 ml) was then added and a vacuum applied until all was drawn through.

Bio-medical applications of high performance liquid chromatography (HPLC) with amperometric detection.

Electrochemical detection of eluted solutes in HPLC is now well established as a selective and highly sensitive technique. Measurement of catecholamines and metabolites has been the most popular application with an exponential increase in literature. Recent improvements include the use of diphenylborate for extractions, the introduction of smaller diameter HPLC materials which improve resolution and sensitivity, and the replacement of carbon paste with glassy carbon which now gives a more stable electrode with similar sensitivity.

Neuropeptide Y and its flanking peptide in human endocrine tumors and plasma.

Neuropeptide Y (NPY) and its flanking peptide (CPON) were measured in extracts of pheochromocytomas (n = 26), ganglioneuroblastomas (n = 8), and other tumors (n = 95) and plasma (n = 38). NPY was present in high concentrations in the majority of the pheochromocytomas, but was absent in 3 tumors. Similar concentrations of NPY were measured using N- and C-terminal-directed antisera, and there was a good correlation between the concentrations of NPY immunoreactivity and CPON immunoreactivity in the same extracts.

Location of extra-adrenal catecholamine secreting tumours by selective venous sampling and nuclear magnetic resonance scanning.

Iodinated meta-iodobenzylguanidine (MIBG) scanning is a safe non-invasive method for locating extra-adrenal paragangliomas. However, a positive result is dependent on the presence of an uptake mechanism in the tumour. We report two cases of MIBG negative intracranial catecholamine secreting tumours successfully located by selective venous sampling and nuclear magnetic resonance scanning.

Effects of two differing halothane concentrations on the metabolic and endocrine responses to surgery.

The effects of two differing concentrations of halothane, 2.1 MAC or 1.2 MAC, on the metabolic and endocrine responses to abdominal hysterectomy were investigated.

The effect of atrial natriuretic peptide on plasma renin activity, plasma aldosterone, and urinary dopamine in man.

The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.

Adrenaline and noradrenaline excretion in placebo treated patients in the Medical Research Council Hypertension Trial and in matched normotensive controls.

The 24-h excretion of adrenaline and noradrenaline was measured in 268 untreated essential hypertensives and in 268 age- and sex-matched controls. No significant difference was found between the groups. However, in the control group alone, a multiple regression analysis showed a highly significant correlation between systolic blood pressure and both noradrenaline (P = 0.

The effect of human atrial natriuretic peptide on urinary sodium and urinary dopamine excretion in man.

Atrial extracts have long been known to produce natriuresis but it is only recently that atrial natriuretic peptide (ANP) itself has been isolated, purified and sequenced. We have now developed a specific radio-immunoassay for ANP and assessed its biological activity by infusing ANP in normal volunteers. Low dose ANP infusion (1.

Urinary catecholamines in essential hypertension: results of 24-hour urine catecholamine analyses from patients in the Medical Research Council trial for mild hypertension and from matched controls.

Four consecutive 24-h urine samples were collected from 134 male and 134 female placebo-treated patients in the Medical Research Council Trial for Mild Hypertension. Similar samples were collected from age and sex-matched normotensive controls. On the fourth day noradrenaline excretion was 22.

Circadian rhythms of epinephrine and norepinephrine in man.

The diurnal rhythms of plasma epinephrine and norepinephrine were investigated in a group of normal young men. Sleep, posture, illumination, and food intake were monitored. Plasma epinephrine demonstrated a statistically significant diurnal rhythm, with a mean amplitude of 14 +/- 1.

The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease.

Studies performed on 18 patients with Parkinson's disease and 6 control subjects have shown that acute administration of L-DOPA in clinically effective doses gives rise to a diffuse increase in regional cerebral blood flow without accompanying stimulation of regional oxygen utilization. The data suggest that this rise in rCBF is caused by vasodilatation due to a direct action of the drug on the cerebral blood vessels. The effect of L-DOPA on rCBF did not correlate with the degree of clinical improvement seen in each patient after treatment.

Reversed-phase high-performance liquid chromatography and amperometric detection of 3-O-methyl isoprenaline sulphate: application to studies on the presystemic metabolism of d-isoprenaline in man.

A selective method for the determination of 3-O-methyl isoprenaline sulphate in human urine and blood plasma has been developed using reversed-phase high-performance liquid chromatography with amperometric detection. The sulphoconjugate was subjected to acidic hydrolysis and the liberated 3-O-methyl isoprenaline was isolated by organic extraction and conventional cation exchange. An internal standard of 3-O-methyl isoetharine was synthesized from commercially available isoetharine and used to correct for recovery losses.

Can the human neonate mount an endocrine and metabolic response to surgery?

Little is known of the ability of the human newborn infant to mount an endocrine and metabolic response to surgical trauma. Blood concentrations of glucose, lactate, pyruvate, alanine, hydroxybutyrate, acetoacetate, and glycerol together with plasma concentrations of insulin, glucagon, adrenaline, and nonadrenaline were measured in 33 infants (26 term, 7 preterm) subjected to surgery during the neonatal period. The results show that newborn infants can indeed mount a substantial endocrine and metabolic stress response, the main features of which are hyperglycemia and hyperlactatemia associated with the release of catecholamines and the inhibition of insulin secretion.