Strategies for increasing drug delivery to the brain: focus on brain lymphoma.

The blood-brain barrier (BBB) is a gate that controls the influx and efflux of a wide variety of substances and consequently restricts the delivery of drugs into the central nervous system (CNS). Brain tumours may disrupt the function of this barrier locally and nonhomogeneously. Therefore, the delivery of drugs to brain tumours has long been a controversial subject.

Abrupt increase of tacrolimus blood levels during an episode of Shigella infection in a child after liver transplantation.

The authors report the case of an 8-year-old girl who underwent a liver transplant at the age of 18 months because of biliary atresia. She was treated with cyclosporin for more than 5 years. Increased hirsutism prompted a change to tacrolimus therapy.

Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators.

Objective: We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged.

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood-brain barrier disruption in patients with brain lymphoma.

Objective: To evaluate the pharmacokinetics of methotrexate in ventricular cerebrospinal fluid and serum after osmotic blood-brain barrier disruption and intra-arterial administration compared with intravenous or simple intra-arterial infusion in patients with primary central nervous system lymphoma.

Methods: Serum and ventricular cerebrospinal fluid were sampled after methotrexate administration in 12 patients. Blood-brain barrier disruption was induced on 2 sequential days by mannitol (25%) infusion delivered to the vertebral or internal carotid artery territories followed by intra-arterial methotrexate (dose, 1.

The effect of short-term dipyrone administration on cyclosporin pharmacokinetics.

Background: A large number of drugs have been shown to affect the metabolism of cyclosporin A (CSA) and, since cyclosporin is characterized by a narrow therapeutic range, the consequences of such drug interactions may often be of clinical importance.

Objective: To evaluate the effect of short-term administration of dipyrone on steady state CSA pharmacokinetics.

Methods: Six kidney- and two heart-transplanted patients on chronic CSA therapy participated in this study, which consisted of two 4-day study periods separated by 3-week washout periods.

Influence of external biliary drainage on cyclosporin A (Neoral) absorption in a pediatric liver transplant recipient.

We report on a patient who underwent a liver transplant 8 yr ago at the age of 2. The post-operative course and further follow-up were uneventful, maintaining immunosuppression with cyclosporin A (CsA) (Sandimmune) and prednisone; 1.5 yr ago, the patient was converted to Neoral.

Systemic absorption of lidocaine after topical application for the treatment of oral mucositis in bone marrow transplantation patients.

This paper evaluates lidocaine absorption via oral mucosa following its topical application for symptomatic treatment of bone marrow transplantation (BMT)-induced oral mucositis. Five patients with high-grade oral mucositis after allogeneic BMT were entered consecutively into the study. Five healthy individuals served as controls.

Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone.

Objective: Dipyrone is a veteran analgesic and antipyretic drug. After oral administration it is rapidly converted by hydrolysis to 4-methylaminoantipyrine (MAA), which is further metabolized to 4-formylaminoantipyrine (FAA), 4-aminoantipyrine (AA) and 4-acetylaminoantipyrine (AAA). It is still debated whether the site of dipyrone action is in the central nervous system or in the periphery.

Cerebrospinal fluid prostaglandins after systemic dipyrone intake.

Objective: The object of this study was to evaluate the time course of thromboxane B2 and prostaglandin E2 concentrations in cerebrospinal fluid after oral administration of dipyrone (INN, metamizole).

Methods: A single 1.0 gm oral dose of dipyrone was given to consenting patients undergoing elective diagnostic lumbar puncture 0.

Digoxin intoxication in a patient with end-stage renal disease: efficacy of digoxin-specific Fab antibody fragments and peritoneal dialysis.

Digoxin intoxication is a serious medical problem, and impairment of renal function is a common risk factor for toxicity. Digoxin specific antibody fragments (Fab) is the most effective treatment available for severe digitalis intoxication. The use of Fab therapy in a patient with renal disease is considered as effective as in patients with normal renal function, although the increased risk of rebound digoxin toxicity mandates a longer period of observation.

Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis B virus.

Background: The pharmacokinetics of a number of drugs has been shown to be impaired in patients with acute or chronic viral liver disease.

Objective: To examine the effect of the asymptomatic hepatitis B virus carrier state on the metabolism of dipyrone (INN, metamizole) as a model drug.

Methods: The pharmacokinetics of the metabolites of dipyrone-4-methylaminoantipyrine, 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine-after a 1.

Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase C-alpha phosphorothioate oligodeoxynucleotide.

Glioblastoma multiforme is the most common form of malignant brain cancer in adults and, unfortunately, is not amenable to treatment with current therapeutic modalities. Human glioblastoma U-87 has many of the distinguishing phenotypic features of primary glioblastoma, including an autocrine form of proliferation, high levels of protein kinase C alpha (PKC alpha), and infiltration via white matter tracts. We show that treatment of mice bearing U-87 xenografts with an antisense phosphorothioate oligodeoxynucleotide (S-oligodeoxynucleotide) against the 3'-untranslated region of PKC alpha mRNA results in suppression of tumor growth.

Carbamazepine pharmacokinetics in obese and lean subjects.

Objective: To compare carbamazepine pharmacokinetic parameters between obese and lean subjects following the administration of a single 200-mg tablet.

Design: Single-dose intervention, open study.

Setting: Teaching university hospital.

Dipyrone metabolism in liver disease.

Background And Objectives: Dipyrone is an analgesic, antipyretic, and anti-inflammatory drug. After oral administration it is hydrolyzed to 4-methylaminoantipyrine and further metabolized to 4-aminoantipyrine, 4-formylaminoantipyrine, and 4-acetylaminoantipyrine. This study investigated the disposition of dipyrone metabolites in 12 hospitalized patients with cirrhosis (age, 25 to 65 years) and 27 healthy subjects of two age groups (young, 21 to 40 years; elderly, 73 to 90 years).

Caffeine pharmacokinetics in obesity and following significant weight reduction.

Objectives: To compare caffeine pharmacokinetics (200 mg single oral dose) between obese and lean subjects and in obese subjects prior to and following weight reduction. In the obese group antipyrine (1000 mg single oral dose) pharmacokinetics were also evaluated one week before caffeine administration.

Setting: Teaching university hospital.

Clinical pharmacokinetics of dipyrone and its metabolites.

The pharmacokinetics of dipyrone are characterised by rapid hydrolysis to the active moiety 4-methyl-amino-antipyrine (MAA), which has 85% bioavailability after oral administration in tablet form, and takes a short time to achieve maximal systemic concentrations (tmax of 1.2 to 2.0 hours).

Multiple drug interactions with cyclosporine in a heart transplant patient.

Objective: To report multiple drug interactions with cyclosporine in a heart transplant recipient.

Case Summary: A 53-year-old man underwent heart transplantation in December 1990. Immunosuppression therapy consisted of prednisone, azathioprine, and cyclosporine 300 mg/d.

Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism.

Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group.

Colchicine disposition in patients with familial Mediterranean fever with renal impairment.

Objective: To assess the pharmacokinetics of serum colchicine in patients with familial Mediterranean fever (FMF) with renal impairment.

Methods: Using a specific radioimmunoassay we determined serum colchicine concentration at various time points following oral administration of a single dose of the drug.

Results: Patients with renal insufficiency had a mean +/- SD apparent total colchicine clearance of 0.

Validity of saliva samples for the estimation of dipyrone metabolites pharmacokinetics.

Plasma and saliva pharmacokinetics of dipyrone (CAS 5907-38-0) metabolites, 4-methylaminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylaminoantipyrine (AAA), has been studied in 10 healthy volunteers, after oral administration of 1.0 g dipyrone, MAA, AA, FAA and AAA saliva concentrations correlated significantly with the respective plasma concentrations (r = 0.81, r = 0.

Intravesical lidocaine: topical anesthesia for bladder mucosal biopsies.

The intravesical instillation of lidocaine solution has been used as a topical form of anesthesia for bladder biopsies. We performed 63 ambulatory procedures in which multiple cold-cup biopsies were obtained during cystoscopy. There was no need for electrocautery.