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PII‐41
Author(s) -
Sarkar M.,
Cronenberger C.,
Mould D.,
Roethig H.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.166
Subject(s) - carboxyhemoglobin , tar (computing) , nonmem , population , pharmacokinetics , chemistry , zoology , anesthesia , medicine , pharmacology , carbon monoxide , environmental health , biochemistry , catalysis , computer science , biology , programming language
BACKGROUND/AIMS Carbon monoxide exposure can be monitored in adult smokers (SM) by determining carboxyhemoglobin (COHb) levels. The purpose of this research was to develop a population based pharmacokinetic model for COHb in SMs. METHODS Data from three open‐labeled randomized controlled studies in SM of 10–30 conventional cigarettes (CC) per day were used. COHb levels were determined in SM at baseline while smoking CC1 (FTC Tar 11 mg) or CC2 (FTC Tar 6 mg), on Days 3 and 8 when randomized to continue smoking CC1 or CC2, switched to another CC3 (FTC Tar 1 mg), or stop smoking. COHb levels were measured at 7am, 11am, 3pm, 7pm and 11pm. Data were analyzed using NONMEM (version V, Level 1.1). Model building and goodness of fit were evaluated using standard methods. The data were best described by a two‐compartment model with zero order input and an endogenous COHb level. The model was parameterized for clearance (CL), central (Vc) and peripheral (Vp) volumes of distribution, inter‐compartmental clearance (Q), baseline COHb (c0), and relative COHb bioavailability (F1). Each cigarette was treated as a unit dose, assuming a linear relationship between cigarettes smoked and measured COHb. RESULTS The half‐lives were estimated at 1.94±0.58 hrs and 15.4±5.38 hrs (alpha and beta phases, respectively). The model suggested COHb F1 increased with increasing FTC Tar, and COHb CL decreased as BW increased. CONCLUSIONS A robust model was developed to (a) predict COHb levels in SM and (b) to determine optimum COHb sampling times. Clinical Pharmacology & Therapeutics (2005) 79 , P47–P47; doi: 10.1016/j.clpt.2005.12.166