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Biomedical subjects

H Breithaupt

Publications and source records attributed to H Breithaupt.

At least 55 records · Page 3Linked to original sources
PubMed1982

Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C).

Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma.

Adult↗
PubMed1982

Determination of mexiletine in biological fluids by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of the anti-arrhythmic drug mexiletine in human plasma, urine, and cerebrospinal fluid is described. Following extraction with diethyl ether, mexiletine and the internal standard 4-methylmexiletine were derivatized with 2,4-dinitrofluorobenzene. Analyses were performed using an alternating on-column enrichment technique on small Perisorb RP-2 30-40 micrometers pre-columns with pre-column backflushing for direct injection onto the analytical column of Spherisorb ODS 5 micrometers. Complete separation from endogenous constituents of plasma, urine or cerebrospinal fluid was achieved by isocratic reversed-phase ion-pair chromatography with 1-heptanesulfonic acid (0.005 M; PIC B7)-acetonitrile-tetrahydrofuran (42:48:10, v/v) as eluent. Interferences from other drugs were not observed. The limit of detection was 10 ng/ml (C.V. 6.5%). Day-to-day coefficients of variation were below 9%. The applicability of this rapid method for pharmacokinetic studies and clinical routine is demonstrated.

Chromatography, High Pressure Liquid↗
PubMed1982

Pharmacokinetics of dacarbazine (DTIC) and its metabolite 5-aminoimidazole-4-carboxamide (AIC) following different dose schedules.

The pharmacokinetics of dacarbazine (DTIC) and its main metabolite 5-aminoimidazole-4-carboxamide (AIC) have been studied in eight patients with malignant melanoma or sarcoma receiving 2.65--6.85 mg DTIC/kg body weight by intravenous bolus injection or by continuous 0.5--6-h infusions on 5 consecutive days. The plasma disappearance of DTIC was biphasic, with a terminal half-life of 41.4 min (range 30.3--51.6 min). The mean distribution volume of DTIC was 0.632 liters/kg and the total clearance was 15.4 ml/kg . min (range 8.7--23.3 ml/kg . min). The renal clearance of DTIC was 5.2--10.9 ml/kg . min, indicating that about 50% of DTIC was eliminated by extrarenal mechanisms. The plasma decay of AIC was mono-exponential with a half-life of 43.0--116 min. A renal clearance of 2.6--5.3 ml/kg . min was calculated for AIC. The urinary recovery was 46%--52% for DTIC and 9%--18% for AIC. The plasma concentrations of DTIC observed during 0.5--6-h infusions of DTIC (5.45--6.85 mg/kg) were 0.66--6.2 micrograms/ml. Comparison of various dosage schedules within the same patient did not reveal relevant differences of the areas under the concentration-time curves. Immunotherapy with Bacillus Calmette-Guérin (BCG) did not significantly influence the pharmacokinetics of DTIC. During isolated extremity perfusion with DTIC (75--130 mg/kg extremity) for treatment of malignant tumors of the extremities concentrations of DTIC ranged from 150--500 micrograms/ml perfusate. There was no evidence of AIC formation. In isolated liver perfusion experiments in anesthetized dogs metabolic degradation of DTIC to AIC was demonstrated.

Adult↗
PubMed1982

Pharmacokinetics of methotrexate and 7-hydroxymethotrexate following infusions of high-dose methotrexate.

The pharmacokinetics of methotrexate (MXT) and 7-hydroxymethotrexate (7-OH-MTX) has been studied in seven patients treated for osteosarcoma with up to 27 cycles of MTX at doses of 140-350 mg/kg of body weight. The distribution volume of MTX was 0.186 +/- 0.062 liter/kg. Peak plasma levels ranged from 540 to 1700 microM for MTX and from 12 to 560 mu M for 7-OH-MTX. The MTX metabolite 2,4-diamino-N10-methylpteroic acid was occasionally detectable in plasma and urine at a level of 10(-7)M. Plasma disappearance of MTX was biphasic, with a terminal half-life of 2.1 +/- 0.6 hours (mean +/- SE). Plasma decay of 7-OH-MTX was mainly monoexponential, with a half-life of 23.8 +/- 15.2 hours. The renal clearance of MTX (0.0623 +/- 0.0232 liter/kg/hour) accounted for about 84% of the total clearance of MTX (0.0742 +/- 0.0288 liter/kg/hour). In urine, 70%-94% of the dose was recovered as MTX and 0.4%-11% as 7-OH-MTX. The renal clearance of 7-OH-MTX was in the range of 0.0173 +/- 0.0149 liter/kg/hour. The pharmacokinetics of MTX and 7-OH-MTX was influenced by orally coadministered activated charcoal, presumably by inhibition of enteral reabsorption of MTX and 7-OH-MTX.

Adolescent↗
PubMed1981

Determination of cytarabine and uracil arabinoside in human plasma and cerebrospinal fluid by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of the antineoplastic agent cytarabine and its main metabolite uracil arabinoside in human plasma and cerebrospinal fluid is described. Complete separation from endogenous constituents was achieved by isocratic reversed-phase chromatography using phosphate buffer (0.05 M, pH 7.0) as the eluent. The limit of detection was 50 ng/ml. Day-to-day coefficients of variation were below 10%. The applicability of this rapid, simple and specific method for pharmacokinetic studies and monitoring of therapy was demonstrated.

Arabinofuranosyluracil↗
PubMed1981

Immunological studies in a case of Evans' syndrome.

Immunological studies in a case of Evans' syndrome (autoimmune hemolytic anemia of the "warm type" associated with idiopathic thrombocytopenic purpura) are presented in whom the autoimmune nature of both conditions was verified by the demonstration of cell-bound and free serum autoantibodies against red blood cells as well as platelets by a radioimmune technique.

Aged↗
PubMed1981

Quantitative high pressure liquid chromatography of 6-thioguanine in biological fluids.

The determination of 6-thioguanine in human plasma and urine is described. By using isocratic reversed-phase high pressure liquid chromatography (HPLC) the purine analogues, 6-thioguanine, guanine, 8-azaguanine, allopurinol, oxipurinol, and uric acid, are completely separated within 8 min. the sensitivity of the assay for 6-thioguanine is 0.2 microgram/ml (1.2 x 10(-6) M) with a precision of 3.7%. The applicability for clinical monitoring in a patient's plasma and urine is demonstrated.

Chromatography, High Pressure Liquid↗
PubMed1980

Post-transfusion thrombocytopenic purpura: immunological and clinical studies in two cases and review of the literature.

Two patients with post-transfusion thrombocytopenic purpura are described, the first cases recognized in Austria and Germany. Both patients were female, 51 and 60 years of age. The purpura was evoked by blood transfusions with a latent period of 2 and 7 days. The thrombocytopenic episode lasted for 22 and 60 days. In one case, thrombocytopenia was associated with agranulocytosis due to transient bone marrow failure. Both patients were negative for the platelet-specific antigen PlA1 (= ZWa). Their sera contained PlA1 as well as potent HLA antibodies. Detailed clinical and serological data are presented. The literature with a total of 25 cases so far reported is surveyed.

Agranulocytosis↗