scholarly journals Volume of Distribution for Dosing Interval Normalized by Surface Area

2020 ◽  
Author(s):  
Keyword(s):  
Surface Area ◽  
Volume Of Distribution ◽  
Dosing Interval

scholarly journals Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Sinziana Cristea ◽  
Anne Smits ◽  
Aida Kulo ◽  
Catherijne A. J. Knibbe ◽  
Mirjam van Weissenbruch ◽  
...  
Keyword(s):  
Perinatal Asphyxia ◽  
Volume Of Distribution ◽  
Stochastic Simulations ◽  
Therapeutic Drug ◽  
Published Data ◽  
Data Set ◽  
Dosing Interval ◽  
Proposed Model ◽  
Dosing Regimens ◽  
The Impact

ABSTRACT Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (>5 mg/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired.

Carbon monoxide disposition in the perfused rat liver

1999 ◽  
Vol 277 (3) ◽  
pp. G725-G730 ◽  
Author(s):  
David G. le Couteur ◽  
Zhan Li Yin ◽  
Laurent P. Rivory ◽  
Allan J. McLean
Keyword(s):  
Carbon Monoxide ◽  
Surface Area ◽  
Rat Liver ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Compartmental Models ◽  
Perfused Rat Liver ◽  
Simple Method ◽  
Area Product ◽  
Apparent Volume Of Distribution

A simple method for determining carbon monoxide (CO) disposition in the rat liver perfused with erythrocyte-free buffer was developed. Wash-in experiments were performed with buffer containing tracer quantities of [14C]sucrose and3H2O and equilibrated with CO. Outflow samples were collected into tubes containing human erythrocytes, which avidly bind CO. Outflow curves were analyzed using compartmental models. Fractional recovery of CO was 1.07 ± 0.17, and the apparent volume of distribution was 1.37 ± 0.30 ml/g of liver ( n = 8). A flow-limited model fitted the data most effectively, although estimates of the permeability-to-surface area product were attempted using a barrier-limited model. This technique will facilitate investigation of the effects of disease on gaseous substrate disposition in perfused organs.

scholarly journals Capillary and cell wall permeability to potassium in isolated dog hearts

1975 ◽  
Vol 229 (3) ◽  
pp. 537-544 ◽  
Author(s):  
RG Tancredi ◽  
T Yipintsoi ◽  
JB Bassingthwaighte
Keyword(s):  
Surface Area ◽  
Volume Of Distribution ◽  
Cell Permeability ◽  
Canine Heart ◽  
Permeability Surface ◽  
The Mean ◽  
Wall Permeability ◽  
Area Product ◽  
Tracer Dilution ◽  
Cell Wall Permeability

From venous tracer-dilution curves recorded after 36 pulse injections of 42KCl and 131I-labeled albumin into the coronary artery inflow of 15 isolated canine heart preparations, we calculated maximal fractional extractions (Emax) and capillary permeability-surface area products (PScap) for 42K+ over a range of plasma flows (FP) from 0.3 to 1.7 ml min-1 g-u. At low FP (less than 1.0), Emax was 0.60 +/- 0.0l (mean +/- SD) and PScap was 0.72 +/- 0.20 ml min-1 g-1; at high FP (greater than 1.0), Emax decreased to 0.49 +/- 0.05 and PScap increased to 1.06 +/- 0.18. Continuous recording (gamma detector) of residual myocardial 42K+ in seven hearts showed that the mean fractional escape rate of tracer between 30 and 60 min after injection was 0.011-0.023 min-1; higher rates were observed at high FP, when the residue of 42K+ decreased to less than 10% of the injected dose by 60 min. Using PScap measured at high FP and considering the virtual intracellular volume of distribution for K+ to be 20 ml/g, we calculated the permeability-surface area product for sarcolemma (PScw) as 0.54-0.73 ml min-1 g-1, or about 50% of PScap. Considering sarcolemmal surface area (Scw) as 4,200 cm2/g and capillary surface area (Scap) as 500 cm2/g, cell permeability is low, with Pcw:Pcap being less than 0.08.

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