Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.

Lack of effect of MICA antibodies on graft survival following heart transplantation.

Little is known about the effect of MICA antibodies (Abs) on cardiac allograft function and survival. Pretransplant and posttransplant serum from 491 and 196 adult cardiac allograft recipients, respectively, has been investigated for MICA Abs, donor specificity and the effect of MICA Abs on graft survival, acute rejection episodes (AR) and cardiac allograft vasculopathy (CAV). Patients with HLA Abs (11.6%) were excluded from the analysis. A total of 11.8% of patients had MICA Abs, without HLA Abs, before their transplant. Actuarial graft survival demonstrated slightly better survival of patients with donor-specific MICA Abs at 1 and 5 years (88.9% and 83.3%) than patients negative for MICA Abs (72% and 63.7%, p = 0.051). After transplantation, 15.8% of patients produced MICA Abs, and in 17 patients these were produced de novo. There was no effect of pretransplant or posttransplant production of MICA Abs on numbers of AR episodes in year 1, or CAV assessed at years 3 and 5. Immunocytochemistry of cardiac biopsies from 11 patients did not demonstrate a presence of MICA. Sera from only 4/69 patients with MICA Abs fixed complement prior to transplantation and from 7/38 patients following transplantation. In conclusion, this study suggests that MICA Abs do not adversely affect the outcome of cardiac transplantation.

[Intestinal B-mode sonography in patients with endemic sprue. Intestinal sonography in endemic sprue]. / Intestinale B-Bild Sonographie bei Patienten mit einheimischer Sprue. Darmsonographie bei einheimischer Sprue.

AIM: The value of ultrasonography in the diagnosis, follow-up and for the detection of complications in patients with celiac sprue has not yet been sufficiently evaluated. A pronounced back and forth motility with echo-rich hump reflexes in a fluid-filled small bowel with a reduction of Kerckring's plicae circulares and with a loss of their density and uniformity was empirically defined as a diagnostic sign of celiac sprue. In the present study, the sonographic signs of celiac sprue were examined as an indicator of active sprue. METHOD: 50 patients with histologically proven celiac sprue were examined with real time ultrasonography (3.5-7 MHz). The detection or exclusion of the defined sonographic signs of celiac sprue with intensified motility and reduction of Kerckring's plicae circulares with a loss of their density and uniformity were evaluated by two independent examiners and documented without knowledge of the clinical findings. The clinical activity (active vs. remission) was assessed according to clinical criteria (diarrhea, steatorrhea, weight loss). 38 healthy subjects and 50 patients with Crohn's disease served as controls. RESULTS: In all 138 patients and controls adequate visualization of the bowel was achieved. In 16/50 (32%) patients with active celiac sprue changes of motility and reduction of Kerckring's plicae circulares with a loss of their density and uniformity were detected, whereas all 34/50 (68%) of patients with celiac sprue in remission did not have this pattern. In none of the controls with Crohn's disease or in the healthy subjects comparative sonographic signs of active celiac sprue were observed. In four patients with active celiac sprue a circumscript echopoor tumor of the small bowel wall could be sonographically detected, which turned out to be T-cell lymphoma in three and a carcinoma of the small intestine in one patient. An increased number of and/or enlarged mesenteric lymph nodes were found in patients with active celiac sprue. CONCLUSION: Changes of motility and reduction of Kerckring's plicae circulares with loss of density and uniformity at ultrasonography are a reliable indicator of active celiac sprue.

[Intestinal ultrasound in rare small and large intestinal diseases]. / Intestinale Sonographie bei seltenen Dünn- und Dickdarmerkrankungen.

Intestinal ultrasonography is a meanwhile established and valid diagnostic method in inflammatory bowel disease, diverticulitis, and appendicitis. Little, however, is known about other more rare intestinal diseases. Serving as a tertiary referral center for a broad spectrum of intestinal diseases we therefore report some aspects of ultrasonography in patients with acute and chronic enteritis and colitis of different origin, e.g., bacterial and viral colitis, ileocecal tuberculosis, AIDS-related enteritis, neutropenic colitis, cystic fibrosis, celiac sprue, vasculitis, benign and malignant tumors of the intestine, amyloidosis, ischemic colitis, and radiogenic enteritis. Ultrasonography may display the transformation of the intestinal wall from normal to pathological states both in inflammatory and neoplastic disease. Besides demonstrating the transmural aspect of inflammation it also shows the mesenteric reaction as well as complications such as fistula, abscesses, stenosis, or ileus. Furthermore, in some diseases intestinal ultrasonography may serve as a diagnostic clue if typical patterns of the bowel wall and impaired peristalsis can be demonstrated. This may lead to an important reduction of invasive and expensive procedures. Ultrasonography is of definite help in the follow-up of inflammatory changes of the bowel wall and primarily diagnostic with respect of other entities (e.g., penicillin-induced segmental hemorrhagic colitis). A sonographic differential diagnosis of diseases of the bowel wall on a purely morphological basis, however, is difficult and rather the exception than the rule. The information gained by ultrasonography regarding intestinal disease, however, is as important and valid as e.g., in case of focal lesions of the liver.

Prediction of carboplatin clearance from standard morphological and biological patient characteristics.

BACKGROUND: Hematologic toxicity of an antineoplastic drug, carboplatin, is largely dependent on its pharmacokinetics. Its therapeutic efficacy may be related to plasma drug exposure. Dosage adjustment based on isotopic determination of glomerular filtration rate has been proposed, but its ambulatory use is not yet conceivable. The dosage adjustment based on a patient's creatinine clearance relies on accurate measurement of urine volume per unit time and can be done with ease. PURPOSE: A population pharmacokinetics study was undertaken to determine a relationship between carboplatin clearance and patient characteristics. A predictive formula was derived that was then prospectively evaluated, and its outcome was compared with that obtained by other methods available to predict carboplatin clearance. METHODS: Plasma carboplatin pharmacokinetics determined as ultrafilterable platinum in 70 patients (age range, 23-84 years) treated with different combination regimens that included carboplatin at doses ranging from 184 mg to 950 mg (1-hour intravenous infusion) for various tumor types. Data were analyzed using the nonlinear mixed effects model (NONMEM). The data from 34 patients (46 cycles) were utilized to derive the most predictive formula. The reliability of the formula was subsequently evaluated by analyzing the data obtained from 36 other patients (49 cycles). RESULTS: Carboplatin clearance (mL/min) was found to be best predicted by the following formula: 0.134.weight + [218.weight.(1-0.00457.age).(1-0.314.sex)]creatinine expressed in micromolar concentration (with weight in kg, age in years, and sex = 0 if male and sex = 1 if female). Prospectively, this formula predicted the carboplatin clearance with good precision (median absolute percent error of 10% [range, 0% to 30%]) and minimal bias (median percent error of 2% [range, -25% to 30%]). This method of prediction was as accurate as the one derived from the measurement of glomerular filtration rate following the injection of 51 chromium-EDTA. CONCLUSION: This formula for the determination of carboplatin clearance can permit individualized determination of carboplatin dosage in adults by simply multiplying the calculated carboplatin clearance by the area under the curve for the desired dosage administration.

A pharmacologically guided phase I study of carboplatin in combination with methotrexate and vinblastine in advanced urothelial cancer.

Carboplatin is an alternative for cisplatin in the treatment of urothelial cancers. A pharmacologically guided phase I study of carboplatin in combination with methotrexate (30 mg/m2) and vinblastine (4 mg/m2) was conducted in ten patients by increment of the area under the plasma concentration versus time curve (AUC) for ultrafilterable carboplatin using the Calvert formula. The maximal tolerated AUC was 5 mg ml-1 min, with neutropenia being the dose-limiting toxicity. There was a significant linear correlation between the percentage of decrease in neutrophil count and the carboplatin AUC. Determination of the glomerular filtration rate by the isotopic method allowed us to adapt the dose of carboplatin given to patients suffering from urothelial cancer, who frequently have impaired renal function. The recommended AUC for phase II study is 4 mg ml-1 min.

[The effect of oral butyl-biguanide on oral glucose tolerance and renal glucose reabsorption in normal human subjects in vivo (author's transl)]. / Die Wirkung oral verabreichten Butyl-Biguanids auf die orale Glucosetoleranz und renale Glucoseresorption (TmG) beim gesunden Menschen in vivo.

1. Oral glucose tolerance in 11 normal subjects was significantly improved after peroral administration of 150 mg of butyl-biguanide. 2. On the other hand maxiumum capacity of renal glucose reabsorption (TmG) and lowest glomerular glucose filtration rate at which glucosuria was recorded (F min) remained uninfluenced after 150 mg of butyl-biguanide in 7 normal subjects. 3. These results are compatible with the hypothesis that the oral administration of therapeutic doses of biguanides yields concentrations at the luminal face of the intestine which inhibit glucose resorption. Plasma concentrations following oral intake of the same dose of biguanide are too low to exert any inhibiting action on renal glucose reabsorption as demonstrated by the present in vivo studies. 4. Urinary flow rate and inulin clearance remained unaltered after butyl-biguanide in these normal subjects.