[Discussion note on: Cefotaxime concentrations in prostatic tissue. Infection 8, suppl. 3 (1980) S 327-S 330; Infection 11 (1983) 33-34].
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Cefotaxime↗
Biomedical subjects
K Seeger
Publications and source records attributed to K Seeger.
Pharmacokinetic properties of the new cephalosporin antibiotic HR 810 in animals.
The pharmacokinetic profile of HR 810 was investigated in mice, rats, rabbits, dogs and monkeys. High blood resp. serum levels were achieved following subcutaneous, intramuscular and intravenous injection, and half-lives ranged from 20 min in mice to 89 min in rabbits. The compound was well distributed in the body and penetrated tissues and body fluids to a high degree. While large amounts of the antibiotic were recovered in the animals' urine, the recovery rate in bile was very low. These good pharmacokinetic properties, together with its high antibacterial activity, open the way for the evaluation of HR 810 in humans.
Animals↗
Determination of cefpirome (HR 810) in serum and urine.
Cefpirome (HR 810) is a new cephalosporin under clinical investigation. Specific and sensitive HPLC- and agar-diffusion methods were developed for the determination of serum- and urine concentrations. The methods are fully validated according to the IFCC Recommendations on Quality Control in Clinical Chemistry. In order to demonstrate the usefulness of both methods, pharmacokinetic profiles of cefpirome after 1 g i.v. administration to human volunteers are presented.
Cephalosporins↗
Chemotherapeutic properties of the new cephalosporin antibiotic HR810 in laboratory animals.
The chemotherapeutic properties of the new aminothiazolyl cephalosporin HR810 were investigated in experimental animals. Unlike other cephalosporins of the third generation, HR810 had good activity against Staphylococcus aureus as well as some activity against enterococci. In murine protection tests with these strains, it was clearly superior to ceftazidime, cefotaxime, ceftriaxone, cefoperazone and latamoxef. The compounds most effective in protecting mice from infections caused by Enterobacteriaceae were HR810 and ceftriaxone followed by ceftazidime, latamoxef and cefotaxime; cefoperazone was less active. HR810 was less active against Pseudomonas aeruginosa than ceftazidime but was considerably more effective than the other cephalosporins tested. HR810 also proved effective against localised infections such as thigh lesions, as well as against meningo-encephalitis in mice and pyelonephritis in rats. These results in laboratory animals make HR810 a promising candidate for clinical studies.
Animals↗
Dose linearity testing of intravenous cefpirome (HR 810), a novel cephalosporin derivate.
After intravenous injection of single doses of 0.25, 0.5, 1.0, 1.5 and 2.0 g of cefpirome (HR 810) to 46 healthy male volunteers in an open manner, concentrations of unchanged drug were estimated at various times in serum and urine, over 24 h and 48 h, respectively. Cefpirome concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay. The measurements obtained were compared by linear distribution independent regression, and were found to be equivalent. A linear relationship between dose and AUC00 (r = 0.96) for both HPLC and microbiological assay was demonstrated for the doses tested (0.25 g to 2.0 g). The biological half-life (t1/2,beta) was determined by fitting a two-compartment open model to the data: t1/2,beta was about 2 h (HPLC, median values) and was not relevantly dose dependent. A general twice daily dosing will be recommended for the treatment of infections. Clinically relevant high concentrations of unchanged cefpirome were detected in urine already after the lowest dose (0.25 g) for about 12 h, and after the highest dose (2.0 g) for at least 24 h. General tolerance was good, only slight temporary taste disturbances immediately after injection were claimed by one volunteer after both 0.5 g and 1.0 g doses and by four volunteers receiving 2.0 g of cefpirome; however, no counter-measures were needed.
Adult↗
Cefotaxime concentrations in prostatic tissue.
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Aged↗
FDG-PET in 10 children with non-Hodgkin's lymphoma: initial experience in staging and follow-up.
BACKGROUND: The use of FDG-PET was evaluated for initial staging and therapy efficacy in paediatric patients with non-Hodgkin's lymphoma (NHL) and compared to the established conventional imaging modalities (CIM). The results of this retrospective analysis are presented in conjunction with a critical review of the current literature. PATIENTS AND METHODS: Ten paediatric patients with NHL were examined using whole-body FDG-PET initially (n = 6), during therapy (n = 5) and after completion of therapy (n = 5), respectively. FDG-PET findings were compared to CIM performed according to the protocol of the German NHL-BFM 95 study. The results were evaluated for their impact on disease classification and therapy decision (St. Jude, REAL) in correspondence to a clinical follow-up of at least 24 months. RESULTS: Concerning initial staging, all lymphoma manifestations detected by conventional imaging were also detected by FDG-PET (15 nodal, 2 extranodal). Furthermore, an additional nodal lesion was detected by FDG-PET in three patients. This resulted in an upstaging followed by an intensified poly-chemotherapy in one patient. In five patients showing unclear residual masses on conventional imaging during therapy, FDG-PET indicated viable residual tumours in one case. This patient showed a relapse during follow-up while the four FDG-PET negative patients did not. After completion of initial therapy, FDG-PET revealed in one out of five patients persistent tumour metabolism in the primary lesions and also detected new manifestations. The patient died shortly after restaging due to disease progression. CONCLUSIONS: These first results on the use of FDG-PET in paediatric non-Hodgkin lymphoma indicate a high potential to improve the therapeutic management.
Adolescent↗
[Clinical applications of the study of immunoglobulin and T-cell receptor gene rearrangements in acute leukemia and non-Hodgkin's lymphoma in children].
In addition to conventional morphological, histological and immunological marker studies, cells from 150 children with leukemia or non Hodgkin's lymphoma were analysed using the Southern blot hybridization technique to examine immunoglobulin- (Ig) and T-cell receptor (TCR) gene rearrangements. Patients with B-lineage leukemia or NHL demonstrated in 90% an Ig heavy chain gene rearrangement, 6% with an additional light chain kappa gene rearrangement. Combined Ig- with TCR-beta-gene rearrangements were mainly found in patients with common ALL: 19% at first presentation, and 33% in relapse. Moreover, 6 c-ALL patients showed rearrangements in all 3 gene loci (JH-, Ck- and TCR). Based on the developmental hierarchy of Ig- and TCR gene rearrangements it was possible to further subclassify c-ALL into different stages of B cell development. No correlation could be established between the different constellations of gene rearrangements, the number of rearranged fragments and the course of illness. All patients with T-lineage leukemia or NHL demonstrated TCR rearrangements of the beta-, g- and delta-gene loci, two with an additional Ig gene rearrangement. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms. Furthermore, non-germline configuration was found in tumor cells of every patient with AUL, O-ALL and AHL, permitting a classification to B- or T-cell lineage. Noteworthy is that every AML patient with Ig- and/or TCR gene rearrangements showed a poor or non-response towards therapy. Specimens of individual patients with differently involved tissues at diagnosis always showed an identical rearrangement. The intensity depended on the number of infiltrating blast cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Marrow Transplantation↗