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Abstract

Z.R. Tayab¹, G. Hochhaus¹, S. Kaufmann², D. Jäger² and J. Barth²

¹Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA, and ²Clinics of the Berufsgenossenschaft Bergmannstrost, Halle, Germany
Objective: In general, the pharmacokinetics (PK) of antibiotics in intensive care unit (ICU) patients are known to differ from healthy subjects. These differences can pose challenges in developing appropriate dosing guidelines. The primary objective of this report was to characterize the disposition of levofloxacin in critically ill patients and to assess any relationships between patient covariates and the PK parameters. Methods: 20 patients in the ICU were given levofloxacin, 500 mg, as an i.v. infusion for a half hour. Plasma samples were taken until 24 hours and assayed using HPLC. The concentration-time data were analyzed using population analysis with NONMEM. Results: The data were described using a 2-compartment model. Creatinine clearance was determined to be a statistically significant predictor of variability in total levofloxacin clearance. For patients with higher levofloxacin clearance, the resulting efficacy for different strains of bacteria (expressed as free AUC/MIC ratios) suggested that for less sensitive pathogens, a dosage adjustment may be needed. Conclusion: A model describing the pharmacokinetics of levofloxacin in critically ill patients was developed. It was determined that creatinine clearance has a significant role in the disposition of levofloxacin. This may have significant implications in the clinical setting for identifying optimal dosage regimens for ICU patients.Correspondence to:
G. Hochhaus, PhD
P.O. Box 100494
Department of Pharmaceutics
College of Pharmacy, JHMHC
University of Florida
Gainesville, FL 32610, USA
Email: [email protected]

Abstract

S. Krishnaswami¹,², G. Hochhaus¹, H. Möllmann³, J. Barth⁴ and H. Derendorf¹

¹Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, ²Pfizer Global R&D, Ann Arbor, MI, USA,
³University of Bochum and ⁴Clinic Bergmannstrost, Halle, Germany
Objective: Reports characterizing the pharmacokinetics of inhaled fluticasone propionate (FP) using compartmental approaches have suggested that the absorption of FP into the systemic circulation is rapid with a half-life of approximately 10 min. We believe that this is a classical case of misassignment of the pharmacokinetic parameter estimates, a problem often encountered while modeling pharmacokinetic data. The objective of this study was to illustrate and analyze this problem using actual blood level data of FP obtained in 14 healthy subjects. Materials and methods: Serum concentration-time data of FP were obtained from a double-blind, randomized study involving single and multiple twice-daily inhalations of 500 mg via a dry powder device, Diskus®. The profiles were fitted using one- and two-compartment pharmacokinetic models with first order absorption. Various permutations of the resulting exponential rate constants were analyzed to determine the combination that was most consistent with the underlying physical process. Results: The two-compartment body model with first order absorption gave excellent fits for the observed FP concentrations after both single and multiple dosing. Even though peak levels were reached relatively early (30 – 90 min) after inhalation, the combination that most appropriately described the underlying process was a > Ka > b, i.e. slow absorption, rapid distribution and slower elimination kinetics. The absorption, distribution and elimination half-lives resulted to be 3.8 h, 9.9 min and 13.6 h, respectively, consistent with the high lipophilicity and sustained dissolution characteristics observed in vitro. Conclusions: Analysis of FP pharmacokinetics after inhalation represents a classical case of potential misassignment of the exponential rate constants, which if ignored, could lead to erroneous interpretations regarding the underlying process. The study also elucidates the pitfall of using tmax to calculate absorption rate.Correspondence to:
H. Derendorf, Ph.D
P.O.Box 100494
Dept. of Pharmaceutics,
College of Pharmacy
University of Florida
Gainesville, FL 32610-0494, USA
Email: [email protected]

Abstract

J. Barth¹,², J. Winkler³, R. Schumann², N.V. Nagaraja³, R. Madabushi³, S. Balbach³, H. Derendorf³, H. Möllmann² and G. Möllenhoff²

¹Medical Clinic Bergmannstrost, Halle, ²Medical Clinic Bergmannsheil,
University of Bochum, Germany, and ³Department of Pharmaceutics,
University of Florida, Gainesville, FL, USA
Objective: High-dose methylprednisolone (MP) is used to treat acute spinal cord injury (ASCI). The objective of the present study was to determine the pharmacokinetics of the pro-drug methylprednisolone hemisuccinate (MPHS) and MP in accident victims with ASCI. Methods: The patients (n = 26) were treated with a bolus intravenous loading dose of 30 mg/kg MPHS within 2 h after injury and this was followed by a maintenance infusion of 5.4 mg/kg/h up to 24 h. Blood, CSF and saliva samples were collected up to 48 h after the initial dose and the samples were analyzed by HPLC. Concentration-time data of MPHS and MP were analyzed using population pharmacokinetic analysis with NONMEM software. Results: MPHS and MP could be monitored in plasma and CSF. MP but not MPHS was present in saliva. High variability was seen in the MPHS levels in CSF. The pharmacokinetics of the pro-drug and the metabolite were adequately described by a 2-compartment model with exponential distribution models assigned to the interindividual and the residual variability. At steady state, the average measured MP concentration in plasma was 12.3 ± 7.0 mg/ml and 1.74 ± 0.85 mg/ml in CSF. The CSF levels of MP could be modeled as a part of the peripheral compartment. Conclusion: This study demonstrated that CSF concentrations of MP were sufficiently high after i.v. administration and reflected the concentrations of unbound drug in plasma. Salivary levels of MP were about 32% of the plasma level and may serve as an easily accessible body fluid for drug level monitoring.
Correspondence to:
PD Dr. J. Barth
BG-Kliniken Bergmannstrost
Merseburger Straße 165
D-06112 Halle/Saale, Germany
Email: [email protected]

Abstract

Nieren- und Hochdruckkrankheiten, Jahrgang 44, Nr. 7/2015, S. 316–320

Diagnostik und interventionelle Therapie des Wunderlich-Syndroms bei Angiomyolipomen im Rahmen eines Morbus Bourneville-Pringle

T. Breining, B. Ammann, S. Dürr und J. Bartholomä

Klinik für diagnostische und interventionelle Radiologie, Universitätsklinikum Ulm, Ulm
Bei Angiomyolipomen handelt es sich um gutartige Raumforderungen der Nieren, die sporadisch oder aber in Zusammenhang mit dem Morbus Bourneville-Pringle (Synonym: Tuberöse Sklerose) auftreten. Eine potenziell lebensbedrohliche Komplikation stellt in diesem Rahmen die spontane Ruptur eines Angiomyolipoms mit konsekutiver retroperitonealer Blutung dar. Diese Konstellation ist auch als sogenanntes Wunderlich-Syndrom bekannt. Im Folgenden berichten wir über eine 44-jährige Patientin mit bekannter tuberöser Sklerose, bei der im Rahmen eines 2-wöchigen stationären Aufenthaltes sowohl die Durchführung CT-graphischer Diagnostik der riesigen Angiomyolipome, als auch die interventionell-radiologische Therapie des Wunderlich-Syndroms entscheidenden Stellenwert besaßen.Correspondence to:
Thomas Breining
Klinik für diagnostische und interventionelle Radiologie
Universitätsklinikum Ulm
Albert-Einstein-Allee 23
D–89081 Ulm
Email: [email protected]

Abstract

Allergologie, Jahrgang 14, Nr. 11/1991, S. 437-439

Kann die nasale Provokation die bronchiale ersetzen?

J. Liepert, H.W. Mollmann und J. Barth

Berufsgenossenschaftliche Krankenanstalten »Bergmannsheil« - Universitätsklinik, Bochum
Im Rahmen der Diagnostik allergischer Atemwegserkrankungen stellen nasale und bronchiale Provokationen einen wichtigen Eckpfeiler zur Überprüfung der Aktualität einer Allergie am betroffenen Zielorgan dar. Zur Beurteilung der Wertigkeit von nasalen Provokationen bei Patienten mit allergischem Asthma bronchiale wurden intraindividuelle Vergleiche nasaler und bronchialer Provokationen mit verschiedenen Allergenen durchgeführt. Es ergaben sich zum einen allergenspezifische Unterschiede: Bei saisonalen Allergenen fand sich eine größere Übereinstimmung beider Verfahren als bei perennialen. Zum anderen war das Ausmaß subjektiv beeinträchtigender Nebenwirkungen bei nasalen Provokationen geringer, und die nasalen Testungen erforderten einen geringeren zeitlichen Aufwand. Daher scheint die nasale Provokation als unkomplizierter Aktualitätsnachweis einer Allergie auch bei Asthmatikern geeignet, sollte aber bei negativem Ausfall und abhängig von der Allergenart durch eine bronchiale Provokation ergänzt werden.Correspondence to:
Dr. med. J. Liepert, Gilsingstraße 14, 4630 Bochum

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