Kinetics membrane disruption due to drug interactions of chlorpromazine hydrochloride.
Drug-membrane interactions assume considerable importance in pharmacokinetics and drug metabolism. Here, we present the interaction of chlorpromazine hydrochloride (CPZ) with supported phospholipid bilayers. It was demonstrated that CPZ binds rapidly to phospholipid bilayers, disturbing the molecular ordering of the phospholipids. These interactions were observed to follow first order kinetics, with an activation energy of approximately 420 kJ mol(-1). Time-dependent membrane disruption was also observed for the interaction with CPZ, such that holes appeared in the phospholipid bilayer after the interaction of CPZ. For this process of membrane disruption, "lag-burst" kinetics was demonstrated.
Nussio
Matthew R
MR
School of Chemistry, Physics and Earth Sciences, and Department of Clinical Pharmacology, Flinders University, Sturt Road, Bedford Park, Adelaide, SA 5001, Australia.
Sykes
Matthew J
MJ
Miners
John O
JO
Shapter
Joseph G
JG
D001665:Binding Sites; D002746:Chlorpromazine / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008567:Membranes, Artificial; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010743:Phospholipids; D002746:Chlorpromazine