Capillary blood sampling for the determination of clozapine concentrations: analytical validation and patient experience.

Patients may be reluctant to start clozapine (CLZ) because of the frequent blood sampling needed for white blood cell monitoring, but also therapeutic drug monitoring of CLZ. Finger prick, instead of venepuncture, might lower the threshold to CLZ use. The aim of this study was to determine whether CLZ concentrations are the same in capillary and venous blood samples.

[John McCrae, physician and poet of "In Flanders Fields"].

During the Second Battle at Ypres (1915), the Canadian medical officer John McCrae was situated in an Advanced Dressing Station in Boezinge, Belgium. Heavily influenced by the suffering of the war he wrote the poem "In Flanders Fields" in May 1915. In this poem he writes about the fallen soldiers who will not rest, until others have taken over the torch of the battle.

[Serotin syndrome; literature overview and Lareb pharmacovigilance reports].

Serotonin syndrome is a medication-induced clinical syndrome, caused by an increased concentration of serotonin in the central and peripheral nervous system. An excess of serotonin can be caused by the use of one or more serotinergic substances on the one hand, or by decreased clearance of these substances on the other hand We carried out a systematic literature search to make an estimation of substances and patient-related factors that might be associated with an increased risk of serotonin syndrome. We also carried out a search for all reports of serotonin syndrome in the Lareb (Netherlands pharmacovigilance centre) database.

Deprescribing in Newly Admitted Psychogeriatric Nursing Facility Patients.

Objective: To determine whether advised changes as a result of structured medication reviews in psychogeriatric patients were implemented and if the implemented changes were maintained.

Design: Prospective cohort study.

Setting: Three nursing facilities in The Netherlands.

The Association Between Potentially Inappropriate Prescribing and Medication-Related Hospital Admissions in Older Patients: A Nested Case Control Study.

Introduction: Medication-related problems can cause serious adverse drug events (ADEs) that may lead to hospitalization of the patient. There are multiple screening methods to detect and reduce potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). Whether this will result in less medication-related hospitalizations is unknown.

Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands.

Unlabelled: OBJECTIVE To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS).

Design: A prospective observational study.

Materials And Methods: We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems.

Drug treatment-related factors of inadequate seizure control.

To optimize seizure control it is important to identify modifiable factors. We conducted a case-control study to explore to what extent drug treatment-related factors are associated with seizures. Eighty-six patients with epilepsy were evaluated: 45 cases (recently experienced a seizure) and 41 controls (seizure-free for at least 2 months).

Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

Objective: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown.

Changes in medication associated with epilepsy-related hospitalisation: a case-crossover study.

Aim: To assess the association between changes in medication and epilepsy-related hospitalisation.

Methods: Data were obtained from the PHARMO Record Linkage System (Jan 1998 to Dec 2002). We conducted a case-crossover study among patients with a first epilepsy-related hospital admission who had continuously used at least one antiepileptic drug (AED) during a 28-week period before admission.

Cyclodextrins in nasal drug delivery.

Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large size and hydrophilicity, resulting in poor transport properties across the nasal mucosa.

Delivery of hormones: some new concepts.

Some new concepts in the delivery of hormones are described. Transmucosal or transdermal penetration of hormones can be facilitated, often by the use of absorption enhancers. Studies of nasal insulin delivery are described.

Intranasal administration of estradiol in combination with progesterone to oophorectomized women: a pilot study.

A pilot study was done to investigate the pharmacokinetics and acceptability of an intranasal 17 beta-estradiol/progesterone formulation. This formulation contained dimethyl-beta-cyclodextrin as a solubilizer and absorption enhancer of the steroid hormones. The study was performed in four oophorectomized and hysterectomized patients.

Intranasal estradiol administration to oophorectomized women.

An open, dose-finding study into the effects of a new intranasal 17 beta-estradiol formulation using dimethyl-beta-cyclodextrin as a solubilizer was conducted in nine hysterectomized and oophorectomized patients with symptoms of estrogen deficiency. After nasal delivery of 0.34 mg estradiol in three patients, concentration-time curves of estradiol in serum and its metabolite estrone in plasma were established.

Nasal absorption enhancement of 17 beta-estradiol by dimethyl-beta-cyclodextrin in rabbits and rats.

A new formulation for nasal administration containing 17 beta-estradiol (E2) with dimethyl-beta-cyclodextrin (DM beta C) as a solubilizer and absorption enhancer is described. Nasal administration of this E2-DM beta C formulation gave a significantly higher E2 absorption than an E2 suspension in both rabbits and rats. Relative to an intravenous injection of the E2-DM beta C formulation, absolute bioavailabilities of 94.

Effects of absorption enhancers on human nasal tissue ciliary movement in vitro.

Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric method, STDHF was found to induce ciliostasis at concentrations of 0.

Stability of amphotericin B in CAPD fluid.

Amphotericin B is the drug of choice in continuous ambulatory peritoneal dialysis (CAPD) associated fungal peritonitis and is usually administered intraperitoneally. The drug is stated to be incompatible with anions. All CAPD fluids contain chloride and lactate anions.

Absorption enhancement of intranasally administered insulin by sodium taurodihydrofusidate (STDHF) in rabbits and rats.

The enhancement of nasal insulin absorption by sodium taurodihydrofusidate (STDHF) was studied in rabbits and rats. Using identical nasal formulations remarkable interspecies differences were observed. The fusidate derivative at 1% (w/v) enhanced nasal insulin bioavailability from 0.

The influence of drugs on nasal ciliary movement.

Drugs in nasal preparations, for local use as well as for systemic use, should not interfere with the self-cleaning capacity of the nose, effectuated by the ciliary epithelium. Many drugs and additives, however, have a negative effect on nasal ciliary function. Examples of ciliotoxic agents are lipophilic and mercuric preservatives, local anesthetics, antihistamines, propranolol, and absorption enhancers such as the bile salts.

New insights into the pharmacokinetics of spironolactone.

Four healthy men took a single oral dose of 200 mg spironolactone after a standardized breakfast. Blood samples were drawn until 24 hours after dosing. A specific HPLC method was used to determine the serum concentrations of spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone, and canrenone.

Determination of the serum concentration of spironolactone and its metabolites by high-performance liquid chromatography.

A simple and rapid high-performance liquid chromatographic assay is described for the simultaneous determination in serum of the aldosterone antagonist spironolactone and its metabolites 7 alpha-thiomethylspirolactone, 6 beta-hydroxy-7 alpha-thiomethylspirolactone and canrenone. Ultraviolet absorption at 240 nm was used to detect the different compounds after elution on a normal-phase column. Endogenous serum substances did not interfere with the assay.