In vivo study of platelet kinetics by75Se-methionine in different haematological disorders

Müller, Ulf; J, Kulinna; Lüber, Jürgen; Hebestreit, H.-P.; Mayer, Manfred M.; Kempgens, U.; er, Wolfgang Quei

doi:10.1007/bf00997036

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…As indicated by the final model with 15 transit compartments, the modeled distribution of life spans for platelets and platelet precursor cells was narrower than that predicted by a monoexponential function discussed previously (20,40). The estimated mean transit times of 7.68 days (CV, 34.7%) for precursor cells and 6.80 days (20.3%) for platelets (Table 2) were in excellent agreement with estimates in the literature for the maturation (approximately 9 days) and life span of platelets (5 to 10 days) (21)(22)(23). The final model described the linezolid-induced thrombocytopenia by an inhibition of the synthesis of platelet precursor cells by linezolid.…”

Section: Discussionsupporting

confidence: 84%

“…A transit compartment approach (20) was employed to describe the life span of platelet precursor cells and platelets. Turnover models with 1, 3, 6, 9, 12, or 15 compartments each for platelet precursor cells (Pre 1 to Pre 15 ) and platelets (PL 1 to PL 15 ) were considered to describe different profiles of the life span distribution for platelets (21)(22)(23). The existence of a larger number of compartments for a specific cell type results in a narrower distribution of platelet life spans for a given patient.…”

Section: Figmentioning

confidence: 99%

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Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid

Boak

Rayner

Grayson

et al. 2014

Antimicrob Agents Chemother

103

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h Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/ liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10-to 28-day therapy for platelet nadirs of <100 ؋10 9 / liter. The risk for toxicity did not differ noticeably between 14 and 28 days of therapy and was significantly higher for patients with lower baseline platelet counts. Due to the increased risk of toxicity after longer durations of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h.

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Section: Discussionsupporting

confidence: 84%

Section: Figmentioning

confidence: 99%

Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid

Boak

Rayner

Grayson

et al. 2014

Antimicrob Agents Chemother

103

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show abstract

“…The patients in the St. Jude series are described as having a rapid rise in platelet counts, but the precise timing was not reported. The normal platelet transit time in the marrow from early megakaryocyte development to the initial appearance of platelets in the blood has been measured at 9.1 days [3]; the rapid correction of platelet counts within only a few days after initiation of iron treatment in the patients might suggest that the defect of thrombopoiesis occurs in a late stage of the process. This is further supported by our previous observation that the bone marrows of many of these patients (3 of 3 in our Chicago series) contain substantial or increased numbers of megakaryocytes [2].…”

Section: M Rubinmentioning

confidence: 98%