Pharmacokinetics of 450 mg ropivacaine with and without epinephrine for combined femoral and sciatic nerve block in lower extremity surgery. A pilot study.

Aims: No pharmacokinetic data exist on doses of ropivacaine larger than 300 mg for peripheral nerve block in man, although in clinical practice higher doses are frequently used. The purpose of the present study was to describe the pharmacokinetic profile in serum of 450 mg ropivacaine with and without epinephrine in patients undergoing anterior cruciate ligament reconstruction.

Methods: Twelve patients were randomly allocated to receive a single shot combined sciatic/femoral nerve block with 60 ml of either ropivacaine 0.

Recovery and long-term renal excretion of propofol, its glucuronide, and two di-isopropylquinol glucuronides after propofol infusion during surgery.

Background: The metabolism of the short-acting anaesthetic agent propofol has been described over the first 24 h. However, the long-term disposition of propofol and its metabolites is unclear. We describe the pharmacokinetics (renal excretion rates and renal clearance) of propofol and its metabolites over 60 h.

Comparison of the effects and disposition kinetics of lidocaine and (+/-)prilocaine in patients undergoing axillary brachial plexus block during day case surgery.

Objective: The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine and prilocaine in two groups of 15 patients undergoing axillary brachial plexus anaesthesia.

Methods: The study had a randomised design. Patients were allocated to one of the two groups of 15.

Clinical pharmacology and the use of articaine for local and regional anaesthesia.

Quicker onset and shorter elimination time favours (+/-) articaine as a short-acting local anaesthetic for regional anaesthesia in day-case settings, e.g. arthroscopy (shoulder, knee), hand and foot surgery, and dentistry, because patients treated with articaine will be 'drug free' more quickly than those who receive other local anaesthetics.

Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside.

High concentrations of enterolignans in plasma are associated with a lower risk of acute coronary events. However, little is known about the absorption and excretion of enterolignans. The pharmacokinetic parameters and urinary excretion of enterodiol and enterolactone were evaluated after consumption of their purified plant precursor, secoisolariciresinol diglucoside (SDG).

Sex-related differences in the pharmacokinetics of isosorbide-5-mononitrate (60 mg) after repeated oral administration of two different original prolonged release formulations.

Objective: To identify differences in the disposition of isosorbide-5-mononitrate between male and female volunteers.

Method: Plasma concentration and area under the concentration-time curve (AUC(SS)) data of isosorbide-5-mononitrate were obtained in a randomized, crossover, multiple-dose bioequivalence study in 24 subjects (12 females and 12 males). Participants received a single oral dose of 60 mg isosorbide-5-mononitrate prolonged-release tablet formulation (formulations I and II) on each of 6 consecutive days.

Lack of male-female differences in disposition and esterase hydrolysis of ramipril to ramiprilat in healthy volunteers after a single oral dose.

The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).

Differences between lovastatin and simvastatin hydrolysis in healthy male and female volunteers:gut hydrolysis of lovastatin is twice that of simvastatin.

The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-beta-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: The group of female volunteers showed a higher yield of the active metabolite beta-hydroxy acid than the group of males (p < 0.

Lack of Male-Female Differences in Disposition and Esterase Hydrolysis of Ramipril to Ramiprilat in Healthy Volunteers after a Single Oral Dose.

The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).

Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of Clavubactin and Synulox in healthy cats.

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin and formulation was B Synulox; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods.

Similar motor block effects and disposition kinetics between lidocaine and (+/-)mepivacaine in patients undergoing axillary brachial plexus block during day case surgery.

The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine (one metabolite) and mepivacaine (two metabolites) in 2 groups of 15 patients undergoing axillary brachial plexus anaesthesia. The study had a randomised design. The 30 patients were divided into 2 groups.

Variable absorption of clavulanic acid after an oral dose of 25 mg/kg of Clavubactin and Synulox in healthy dogs.

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in dogs, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single dose in an open, randomized, two-way crossover study involving 24 male Beagle dogs treated with two Amoxi-Clav formulations (A Clavubactin and B Synulox, each with 200/50 mg). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods.

Steady state bupivacaine plasma concentrations and safety of a femoral "3-in-1" nerve block with bupivacaine in patients over 80 years of age.

Objectives: Fracture of the upper femur is a common injury in the elderly. Several anesthetic techniques exist for surgery of traumatic hip fracture. The aim of this investigation was to study plasma concentrations and safety of 2 mg/kg bupivacaine in a femoral "3-in-1" nerve block in patients older than 80 years of age.

Identical pattern of highly variable absorption of clavulanic acid from four different oral formulations of co-amoxiclav in healthy subjects.

The aims of this investigation were to calculate the pharmacokinetic parameters of amoxicillin and clavulanic acid, and to identify parameters that may affect their observed differences in absorption. Data were obtained from plasma concentration-time curves from four different open, randomized, two-treatment, two-period, two-sequence, crossover Phase I bioequivalence studies, with the following co-amoxiclav formulations: tablets 250/125, 500/125 and 875/125 mg, or 10 mL of an oral suspension 250/62.5 mg per 5 mL.

Skeletal muscle relaxants: pharmacodynamics and pharmacokinetics in different patient groups.

Muscle relaxants can be safely administered during anaesthesia, providing the basic pharmacodynamic and pharmacokinetic characteristics of the compounds together with the physiological status of the patient are known. In this review the pharmacodynamics and pharmacokinetics of the neuromuscular blocking agents are discussed and related to the physical health or disease state of groups of patients.

Liver and gut mucosa acetylation of mesalazine in healthy volunteers.

Aim: The aim of this investigation was to identify which part of a dose mesalazine is acetylated by enzymes in the gut wall during the absorption process, and which part by the liver enzymes after absorption.

Method: This study was based on data from four bioequivalence studies of different formulations of tablets (gastro-resistant single dose 500 mg (n = 24) and prolonged-release tablets (single dose 1000 mg, n = 18; multiple dose 1000 mg t.i.

Codeine analgesia is due to codeine-6-glucuronide, not morphine.

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine.

Mono- and biphasic plasma concentration-time curves of mesalazine from a 500 mg suppository in healthy male volunteers controlled by the time of defecation before dosing.

This study was based on data from a bioequivalence study (n=24) of two different formulations of suppositories containing 500 mg mesalazine (formulation I and II), with a similar dissolution profile in phosphate buffer pH 6.8. There was a large intra- and intersubject variability in the plasma concentration-time curves of mesalazine from both suppositories.

Bioavailabilities of quercetin-3-glucoside and quercetin-4'-glucoside do not differ in humans.

The flavonoid quercetin is an antioxidant which occurs in foods mainly as glycosides. The sugar moiety in quercetin glycosides affects their bioavailability in humans. Quercetin-3-rutinoside is an important form of quercetin in foods, but its bioavailability in humans is only 20% of that of quercetin-4'-glucoside.

Similar motor block effects with different disposition kinetics between lidocaine and (+ or -) articaine in patients undergoing axillary brachial plexus block during day case surgery.

Aim: The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine and articaine in two groups of 15 patients undergoing axillary brachial plexus anesthesia.

Method: The study had a randomized design. Thirty patients were allocated to one of the two groups.

High-performance liquid-chromatographic-atmospheric-pressure chemical-ionization ion-trap mass-spectrometric identification of isomeric C6-hydroxy and C20-hydroxy metabolites of methylprednisolone in the urine of patients receiving high-dose pulse therapy.

Fourteen metabolites of methylprednisolone have been analysed by gradient-elution high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The compounds were separated on a Cp Spherisorb 5 microm ODS column connected to a guard column packed with pellicular reversed phase. The mobile phase was an acetonitrile- 1.

High-performance liquid chromatography analysis, preliminary pharmacokinetics, metabolism and renal excretion of methylprednisolone with its C6 and C20 hydroxy metabolites in multiple sclerosis patients receiving high-dose pulse therapy.

A gradient eluent HPLC analysis in human plasma and urine was developed and validated for methylprednisolone (MP), its prodrug methylprednisolone-21-hemisuccinate (MPS) with the metabolites 6beta-hydroxy-6alpha-methylprednisolone (MPA), 20-hydroxymethylprednisolone (MPC), 6beta-hydroxy-20alpha-hydroxymethylprednisolone (MPB), 6beta-hydroxy-20beta-hydroxymethylprednisolone (MPE), 20-carboxymethylprednisolone (MPD), methylprednisolone-glucuronide (MPF) and 21-carboxymethylprednisolone (MPX). The column was Cp Spherisorb C8 5 microm, 250 mm x 4.6 mm I.

Absolute bioavailability, pharmacokinetics, renal and biliary clearance of distigmine after a single oral dose in comparison to i.v. administration of 14C-distigmine-bromide in healthy volunteers.

Aim: The aim of the study was to determine the absolute bioavailability and pharmacokinetics after a single dose oral administration in comparison to i.v. administration of 14C-labelled distigmine-bromide (14C-Ubretid) in healthy male volunteers.

Isolation and identification of the C6-hydroxy and C20-hydroxy metabolites and glucuronide conjugate of methylprednisolone by preparative high-performance liquid chromatography from urine of patients receiving high-dose pulse therapy.

In the present study metabolites of methylprednisolone were detected using gradient elution high-performance liquid chromatography. Separation was performed by a Cp Spherisorb ODS 5 microm (250 mmx4.6 mm I.

Clinical consequences of the biphasic elimination kinetics for the diuretic effect of furosemide and its acyl glucuronide in humans.

This review discusses the possibility of whether furosemide acyl glucuronide, a metabolite of furosemide, contributes to the clinical effect of diuresis. First an analytical method (e.g.