{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:47:09Z","timestamp":1784692029410,"version":"3.55.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Liposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population. The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk-stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB (\n            <jats:italic>n<\/jats:italic>\n            = 17; 3 mg\/kg once a day [QD]), CAS (\n            <jats:italic>n<\/jats:italic>\n            = 19; 50 mg QD; day 1, 70 mg), or the combination of both (CAS-LAMB;\n            <jats:italic>n<\/jats:italic>\n            = 17) for a median duration of 10 to 13 days (range, 4 to 28 days) until defervescence and granulocyte recovery. PK sampling was performed on days 1 and 4. Drug concentrations in plasma (LAMB, 405 samples; CAS, 458 samples) were quantified by high-pressure liquid chromatography and were analyzed using population pharmacokinetic modeling. CAS concentration data best fitted a two-compartment model with a proportional error model and interindividual variability (IIV) for clearance (CL) and central volume of distribution (\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            ) (CL, 0.462 liter\/h \u00b1 25%;\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            , 8.33 liters \u00b1 29%; intercompartmental clearance [\n            <jats:italic>Q<\/jats:italic>\n            ], 1.25 liters\/h; peripheral volume of distribution [\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>2<\/jats:sub>\n            ], 3.59 liters). Concentration data for LAMB best fitted a two-compartment model with a proportional error model and IIV for all parameters (CL, 1.22 liters\/h \u00b1 64%;\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            , 19.2 liters \u00b1 38%;\n            <jats:italic>Q<\/jats:italic>\n            , 2.18 liters\/h \u00b1 47%;\n            <jats:italic>V<\/jats:italic>\n            <jats:sub>2<\/jats:sub>\n            , 52.8 liters \u00b1 84%). Internal model validation showed predictability and robustness of both models. None of the covariates tested (LAMB or CAS comedication, gender, body weight, age, body surface area, serum bilirubin, and creatinine clearance) further improved the models. In summary, the disposition of LAMB and CAS was best described by two-compartment models. Drug exposures in aHSCT patients were comparable to those in other populations, and no PK interactions were observed between the two compounds.\n          <\/jats:p>","DOI":"10.1128\/aac.00265-11","type":"journal-article","created":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T19:06:06Z","timestamp":1321383966000},"page":"536-543","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Population Pharmacokinetics of Liposomal Amphotericin B and Caspofungin in Allogeneic Hematopoietic Stem Cell Recipients"],"prefix":"10.1128","volume":"56","author":[{"given":"Gudrun","family":"W\u00fcrthwein","sequence":"first","affiliation":[{"name":"Centre for Clinical Trials Muenster, University Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Young","sequence":"additional","affiliation":[{"name":"Centre for Clinical Trials Muenster, University Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lanvers-Kaminsky","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, University Children's Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Hempel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, University Children's Hospital Muenster, Muenster"},{"name":"Department of Pharmaceutical and Medical Chemistry\u2013Clinical Pharmacy, University of Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam N.","family":"Trame","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, University Children's Hospital Muenster, Muenster"},{"name":"Department of Pharmaceutical and Medical Chemistry\u2013Clinical Pharmacy, University of Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Schwerdtfeger","sequence":"additional","affiliation":[{"name":"Center for Blood Stem Cell and Bone Marrow Transplantation, Deutsche Klinik fuer Diagnostik Wiesbaden, Wiesbaden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Ostermann","sequence":"additional","affiliation":[{"name":"Center for Bone Marrow Transplantation, Department of Internal Medicine II, University Hospital Grosshadern, Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner J.","family":"Heinz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver A.","family":"Cornely","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Clinical Trials Centre Cologne, ZKS K\u00f6ln, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and Centre for Integrated Oncology, CIO K\u00f6ln-Bonn, University of Cologne, Cologne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedwig","family":"Kolve","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Boos","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, University Children's Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerda","family":"Silling","sequence":"additional","affiliation":[{"name":"Center for Bone Marrow Transplantation and Department of Internal Medicine, University Hospital Muenster, Muenster"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, University Children's Hospital Muenster, Muenster, Federal Republic of Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199610000-00014"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/323335"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.828-833.2002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/BF00685732","article-title":"The kinetics of the auto-induction of ifosfamide metabolism during continuous infusion","volume":"36","author":"Boddy AV","year":"1995","unstructured":"BoddyAV ColeM PearsonAD IdleJR. 1995. The kinetics of the auto-induction of ifosfamide metabolism during continuous infusion. Cancer Chemother. Pharmacol. 36:53\u201360.","journal-title":"Cancer Chemother. Pharmacol"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s11046-009-9196-6","article-title":"Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician's viewpoint","volume":"168","author":"Bow EJ","year":"2009","unstructured":"BowEJ. 2009. Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician's viewpoint. Mycopathologia 168:283\u2013297.","journal-title":"Mycopathologia"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23109"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/514341"},{"key":"e_1_3_3_10_2","unstructured":"EMEA. 2008. 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