HES 130/0. 42 shows less alteration of pharmacokinetics than HES 200/0

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HES 130/0. 42 shows less alteration of pharmacokinetics than HES 200/0 HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly† G.B. Lehmann, F. Asskali, M. Boll, M.A. Burmeister, G. Marx, R. Hilgers, H. Förster British Journal of Anaesthesia Volume 98, Issue 5, Pages 635-644 (April 2007) DOI: 10.1093/bja/aem068 Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 1 Time course of HES serum concentration (a) during repeated administration of HES 130/0.42 or HES 200/0.5, respectively, on five consecutive days and cumulative HES recoveries in the urine (b). Healthy volunteers were given daily doses of 50 g HES over 4 h. Urinary HES recovery is expressed as per cent of the cumulative dose of HES from treatment start to the end of the respective treatment day and shows no significant between-group differences. British Journal of Anaesthesia 2007 98, 635-644DOI: (10.1093/bja/aem068) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 2 Change over time of various pharmacokinetic coefficients during repeated administration on five consecutive days of HES 130/0.42 or HES 200/0.5, respectively. (a) Area under the HES concentration curve (AUC0–24 h) anova LD_F2: treatment P < 0.0001, time P < 0.0001, interaction P < 0.0001; (b) maximal HES concentration (Cmax) anova LD_F2: treatment P < 0.0001, time P < 0.0001, interaction P = 0.0107; and (c) elimination half-life (t1/2) anova LD_F2: treatment P < 0.0001, time P < 0.0001, interaction P = 0.2338. Healthy volunteers were given daily doses of 50 g HES over 4 h. With each of the interactions of the coefficients, time and solution effects are significant (P < 0.0001; anova). British Journal of Anaesthesia 2007 98, 635-644DOI: (10.1093/bja/aem068) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 3 Time profiles of haemoglobin concentration (a) and the corresponding relative blood volume change (b) during repeated administration on five consecutive days of HES 130/0.42 or HES 200/0.5, respectively. Healthy volunteers were given daily doses of 50 g of HES over 4 h. For haemoglobin concentration, overall there are decreases in both groups (HES 130/0.42: P = 0.0077; HES 200/0.5: P = 0.0455; sign-test for individual regression coefficients); no significant differences, however, exist between the groups (P = 0.2943; paired t-test for individual regression coefficients). No significant trends or between-group differences are obvious for change of blood volume. British Journal of Anaesthesia 2007 98, 635-644DOI: (10.1093/bja/aem068) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 4 Time profiles of COP (a), plasma viscosity (b), and α-amylase activity (c) during repeated administration on five consecutive days of HES 130/0.42 or HES 200/0.5, respectively. Healthy volunteers were given daily doses of 50 g HES over 4 h. The overall increase in α-amylase activity is significant with HES 200/0.5 (P = 0.0077; sign-test for individual regression coefficients) but not with HES 130/0.42 (P = 0.7237). Paired t-test reveals a significant between-group difference (P < 0.0001). British Journal of Anaesthesia 2007 98, 635-644DOI: (10.1093/bja/aem068) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions