Population pharmacokinetic/pharmacodynamic modeling of histamine response measured by histamine iontophoresis laser Doppler.
The epicutaneous histamine (EH) test is the current gold standard method for the clinical evaluation of allergic conditions. However, the EH method is limited in providing an objective and qualitative assessment of histamine pharmacodynamic response. The histamine iontophoresis with laser Doppler (HILD) monitoring method, an alternative method, allows a fixed dose of histamine to be delivered and provides an objective, continuous, and dynamic measurement of histamine epicutaneous response in children and adults. However, due to the high sampling frequency (up to 40 Hz), the output files are usually too cumbersome to be directly used for further analysis. In this study, we developed an averaging algorithm that efficiently reduces the HILD data in size. The reduced data was further analyzed and a population linked effect pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the local histamine response. The model consisted of a one-compartment PK model and a direct-response fractional maximum effect (Emax) model. The parameter estimates were obtained as follows: absorption rate constant (ka), 0.094/min; absorption lag time (Tlag), 2.72 min; partitioning clearance from local depot to systemic circulation (CLpar), 0.0006 L/min; baseline effect (E0), 13.1 flux unit; Emax, 13.4; concentration at half maximum effect (EC50) 31.1 mg/L. Covariate analysis indicated that age and race had significant influence on Tlag and EC50, respectively.
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Xiaoxi
X
Liu
Department of Pediatrics, University of Missouri School of Medicine, Kansas City, MO, USA.|Division of Pediatric Pharmacology and Medical Toxicology, Children's Mercy Hospital, Kansas City, MO, USA.|Division of Allergy Asthma and Immunology, Children's Mercy Hospital, Kansas City, MO, USA.
Bridgette L
BL
Jones
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Jessica K
JK
Roberts
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA. catherine.sherwin@hsc.utah.edu.|Department of Pharmacology and Toxicology, University of Utah College of Pharmacy, Salt Lake City, UT, USA. catherine.sherwin@hsc.utah.edu.
Catherine M
CM
Sherwin
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001783:Blood Flow Velocity; D002648:Child; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008297:Male; D008954:Models, Biological
D006633:Histamine Antagonists; D006632:Histamine
Data averaging algorithm; Histamine iontophoresis with laser Doppler; Histamine pharmacodynamics; PK/PD linked effect modeling