Pulmonary Disposition and Pharmacodynamics of Verapamil

Evaluation of non‐respiratory function of the human lung by HIPDM lung scanning

“…The pulmonary uptake of basic amines is saturable but, unlike that described for endogenous biogenic amines, does not involve a carrier-mediated, energy-requiring transport system (Junod, 1972;Anderson et al, 1974;Dollery & Junod, 1976;Philpot et al, 1977). imipramine, methadone, chlorphentermine, propranolol, verapamil, and amiodarone are stored by the lungs in a slowly effluxable pool (Eling et al, 1975;Wilson et al, 1976;Philpot et al, 1977;Blanck & Gillis, 1979;Wilson et al, 1979;Gillespie et al, 1984;Camus ef al., 1990). Basic amines with amphiphilic character, e.g.…”

Mitochondria act as a reservoir for the basic amine HIPDM in the lung

“…Thus, in the rabbit lung, a sizeable fraction of HIPDM is retained in a slowly effluxable pool. The formation of a slowly effluxable pool has been described, in isolated-perfused lungs, for a variety of basic amines [8][9][10][11]14]. In these experiments, the size of the slowly effluxable pool was similar to that observed for HIPDM, ranging 30-55% of the drug accumulated by the lungs [8,9,11,14].…”

“…The formation of a slowly effluxable pool has been described, in isolated-perfused lungs, for a variety of basic amines [8][9][10][11]14]. In these experiments, the size of the slowly effluxable pool was similar to that observed for HIPDM, ranging 30-55% of the drug accumulated by the lungs [8,9,11,14]. For imipramine, a pulmonary persistent pool with a mean residence time in excess of 5 h has also been demonstrated in vivo in rabbits receiving i.v.…”

“…The available data on the pharmacokinetic function of the lung can be summarized as follows: 1) the compounds which concentrate most extensively in the lungs are amines with a pKa greater than 8, collectively grouped under the term of basic amines [1,2]; 2) many of these molecules are amphiphilic in nature, inasmuch as they contain a large hydrophobic group and a side chain which is protonated at physiological pH [1,2]; 3) in contrast to endogenous biogenic amines [3], a carrier-mediated, energy-dependent transport system is not involved in the pulmonary uptake of basic amines [4][5][6]; 4) no appreciable in vivo lung metabolism has been reported for most of the basic amines investigated so far [4,[6][7][8][9][10][11][12]; 5) basic amines with amphiphilic character, e.g. imipramine [8,13], methadone [9,13], chlorphentermine [13], propranolol [10], verapamil [11], and amiodarone [14], are retained in the lungs in a slowly effluxable pool. At present, there is no obvious explanation for the observed persistence of these drugs in the lungs.…”

Effects of smoking on the lung accumulation of [11C]McN5652

“…The lung has 5-HTT and its role in pulmonary hypertension has been reported [6]. In addition, the lung is also reported to have a mechanism of uptake for amines [7][8][9][10][11][12][13]. (+)McN5652 has high affi nity to 5-HTT (Ki = 1.25 nM) [4], whereas (−)McN5652 is inactive for 5-HTT (Ki = 912 nM) [4] and is used to evaluate nonspecifi c binding in the brain [14].…”