Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort (budesonide/formoterol) pressurized metered dose inhaler.

Introduction: Many patients with chronic obstructive pulmonary disease or asthma experience difficulties in coordinating inhalation with pressurized metered-dose inhaler (pMDI) actuation. The use of a spacer device can improve drug delivery in these patients. The aim of this study was to establish the relative bioavailability of single doses of Symbicort (budesonide/formoterol) pMDI 160/4.

A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.

Aims: Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM.

Methods: Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography.

A novel mutation in the biliverdin reductase-A gene combined with liver cirrhosis results in hyperbiliverdinaemia (green jaundice).

Background: Hyperbiliverdinaemia is a poorly defined clinical sign that has been infrequently reported in cases of liver cirrhosis or liver carcinoma, usually indicating a poor long-term prognosis.

Aims: To clarify the pathogenesis of hyperbiliverdinaemia in an extended case report.

Methods: A 64-year-old man with alcoholic cirrhosis was admitted to hospital with severe bleeding from oesophageal varices.

Determination of nebulizer droplet size distribution: a method based on impactor refrigeration.

Size distributions of droplets generated by nebulizers are difficult to determine because of evaporation after aerosolization. We describe a method whereby a Next Generation Pharmaceutical Impactor (NGI; MSP Corporation, Shoreview, MN) is refrigerated at 5 degrees C before connecting it to the nebulizer in order to ensure an environment inside the NGI at close to 100% relative humidity (RH). This, in turn, reduces droplet evaporation between the nebulizer and impaction.

CYP2D6 genotype in relation to perphenazine concentration and pituitary pharmacodynamic tissue sensitivity in Asians: CYP2D6-serotonin-dopamine crosstalk revisited.

Objectives: Hyperprolactinemia is a common side effect of first-generation antipsychotics mediated by antagonism of dopaminergic neurotransmission in the pituitary. Most first-generation antipsychotics are metabolized by CYP2D6 in the liver. Further, CYP2D6 is expressed in the human brain as a 5-methoxyindolethylamine O-demethylase potentially contributing to regeneration of serotonin from 5-methoxytryptamine.

Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study.

Background: The way various antiretroviral drugs and drug combinations affect HIV-1 infection in the central nervous system is still largely unknown. The aim of this study was to determine the cerebrospinal fluid (CSF) steady-state concentrations of saquinavir and nelfinavir in relation to plasma concentrations, and to study their effect in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal immunoactivation, and blood-brain barrier integrity.

Methods: Paired CSF and plasma samples from 8 antiretroviral-naïve HIV-1 infected patients starting combination therapy with saquinavir, nelfinavir, and two nucleoside analogues were collected prior to treatment, and again after approximately 12 and 48 weeks of antiretroviral therapy.

The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment.

Objectives: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy.

Alprazolam as a probe for CYP3A using a single blood sample: pharmacokinetics of parent drug, and of alpha- and 4-hydroxy metabolites in healthy subjects.

Objectives: (1) To determine the pharmacokinetic parameters of alprazolam and its two metabolites in plasma from healthy volunteers; (2) to identify a suitable single time point to take a plasma sample for CYP3A phenotyping.

Methods: Twelve healthy Swedish volunteers received a single oral dose of 1 mg alprazolam. Blood samples were collected before drug intake and frequently up to 72 h thereafter.

Simultaneous quantification of alprazolam, 4- and alpha-hydroxyalprazolam in plasma samples using liquid chromatography mass spectrometry.

A sensitive and specific method was developed for quantification of alprazolam and its two metabolites 4-hydroxyalprazolam and alpha-hydroxyalprazolam in plasma. The work up procedure was solid phase extraction. Liquid chromatography-mass spectrometry (LC-MS) was used for separation, detection and quantification of the analytes.

Determination of phenprocoumon, warfarin and their monohydroxylated metabolites in human plasma and urine by liquid chromatography-mass spectrometry after solid-phase extraction.

A high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for the quantification of phenprocoumon, warfarin, and their known monohydroxylated metabolites in human plasma and urine was developed using a simple, selective solid-phase extraction scheme. Chromatographic separation was achieved on a reversed-phase Luna C18 column and step gradient elution resulted in a total run time of about 13 min. Limits of quantification (LOQ) were < or = 40 nM for the parent compounds and < or = 25 nM for the metabolites and the limit of detection (LOD) was < or = 2.

Efavirenz plasma concentrations in HIV-infected patients: inter- and intraindividual variability and clinical effects.

Efavirenz is a drug subject to extensive metabolism, mainly by the cytochrome P-450 isoenzyme CYP2B6, known to exhibit extensive interindividual variability. The aim of the present study was 2-fold: to investigate the relationship between plasma concentration and clinical effects of efavirenz and to investigate the extent of the inter- and intraindividual variability of the plasma concentration measurements. From an open clinic, 68 HIV-positive patients on efavirenz-containing treatment were recruited.

Comparison of the antinociceptive effect of morphine, methadone, buprenorphine and codeine in two substrains of Sprague-Dawley rats.

Sprague-Dawley rats from two different vendors, Möllegård, Denmark and B&K Universal, Sweden, have been tested for the antinociceptive effect of morphine, methadone, buprenorphine and codeine on the hot plate. Morphine and methadone had significantly weaker effect in Möllegård rats compare to B&K rats. In contrast, the effect of buprenorphine was stronger in Möllegård rats than in B&K rats and the effect of codeine was similar in the two substrains.

A simple pharmacokinetic method to evaluate the pulmonary dose in clinical practice--analyses of inhaled sodium cromoglycate.

When the expected effect of an inhaled drug is not achieved, the cause could be poor inhalation technique and consequently a low pulmonary dose. A simple in vivo test to evaluate the pulmonary dose would be a benefit. This study evaluates the relative and systemic bioavailability following inhalation of nebulized sodium cromoglycate (SCG) in healthy subjects.

[A case report. Unconscious patient with neon yellow skin was intoxicated with dipyridamole].

A 66-year old man called for an ambulance from his home because of acute chest pain. When the crew arrived he was unresponsive and hypotensive. Sublingual nitroglycerine was given and subsequently the patient collapsed into circulatory failure and respiratory arrest.

Interpretation of the presence of 6-monoacetylmorphine in the absence of morphine-3-glucuronide in urine samples: evidence of heroin abuse.

The presence of morphine in a urinary sample may be caused not only by intake of heroin but also by intake of poppy-seed-containing food shortly before urine sampling or intake of drugs containing morphine, ethyl morphine, or codeine. To facilitate the interpretation, the heroin-specific metabolite 6-monoacetylmorphine (6-MAM) can be analyzed along with morphine-3-glucuronide (M3G) in an LC-MS verification analysis. In sporadic samples positive in the immunologic opiate screening test, 6-MAM, but not M3G, was found.

High serum concentrations of the acyclovir main metabolite 9-carboxymethoxymethylguanine in renal failure patients with acyclovir-related neuropsychiatric side effects: an observational study.

Background: Acyclovir (ACV) has been used for over two decades to treat herpes virus infections. Serious neurological adverse side effects have occurred during ACV treatment in patients with renal failure, but the cause of the symptoms remains unknown. We hypothesized that increased concentrations of the ACV main metabolite 9-carboxymethoxymethylguanine (CMMG) correlated to these symptoms.

Maintenance therapy with zuclopenthixol decanoate: associations between plasma concentrations, neurological side effects and CYP2D6 genotype.

Rationale: Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established.

Objective: To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate.

[Guidelines for management of patients with pancreatic cancer].

The incidence of pancreatic cancer has fallen during the last ten years in Sweden. Early signs and symptoms of the disease are still undiscovered and when diagnosis is made the disease is incurable in most patients. Transabdominal ultrasonography is the first-line imaging test followed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) if required for definite diagnosis.