Isolation of urinary p-hydroxylated metabolites of mephentermine and phentermine in male Wistar rats. Freeze-fracture studies of cytoplasmic inclusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs. Pharmacokinetics of amiodarone in the isolated rat lung. Ionamin online references

Ionamin online research references

Xenobiotica. 1990 Jul;20(7):653-6.
Isolation of urinary p-hydroxylated metabolites of mephentermine and phentermine in male Wistar rats.

Mori MA, Uy-Yu N, Sakai K, Inoue M, Miyahara T, Kozuka H.

Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.

1. p-Hydroxymephentermine (p-hydroxy-MP) and p-hydroxyphentermine (p-hydroxy-Ph) were isolated as hydrochlorides from urine of male Wistar rats repeatedly dosed with mephentermine (MP). In addition, p-hydroxy-Ph was isolated as the hydrochloride from urine of the rats dosed with phentermine (Ph). 2. These results substantiate previous indications that p-hydroxylation of MP and Ph was a primary metabolic reaction in the rat.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2238700&dopt=Abstract

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Biochim Biophys Acta. 1979 Oct 26;575(1):71-80.
Freeze-fracture studies of cytoplasmic inclusions occurring in experimental lipidosis as induced by amphiphilic cationic drugs.

Buchheim W, Drenckhahn D, Lullmann-Rauch R.

The ultrastructure of cytoplasmic inclusions, which characterize experimental lipidosis as induced by several amphiphilic cationic drugs, was studied by means of freeze-fracturing and thin-sectioning. Retinal and adrenal tissues of rats chronically treated with high oral doses of chlorphentermine were used. In thin sections the cytoplasmic inclusions, which were previously shown to represent lysosomes overloaded with polar lipids, exhibit lamellated or lattice-like internal patterns. The present freeze-fracture observations are interpreted as to indicate that the lamellated inclusions contain polar lipids in the lamellar phase, whereas those with lattice-like patterns contain polar lipids in a hexagonal phase.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=228737&dopt=Abstract

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J Pharmacol Exp Ther. 1990 Jul;254(1):336-43.
Pharmacokinetics of amiodarone in the isolated rat lung.

Camus P, Coudert B, D'Athis P, Dumas M, Escousse A, Jeannin L.

Service de Pneumologie et de Reanimation, Centre Hospitalier Universitaire, Dijon, France.

In these studies we examined the kinetics of amiodarone (Am) uptake and efflux in/from the lung, and the influence of other amphiphilics on these processes. We used single-pass perfused isolated lungs from rats. Medium containing Am (30 microM + 1 microCi of [14C]Am) was perfused through the lung for 20 min (uptake), followed by 20 min of perfusion with drug-free medium (efflux). Lack of metabolism enabled us to follow Am by measuring the amount of radioactivity in perfusate and lung. Other concentrations of Am (3, 60 and 120 microM; n = 2-4 each) were also examined. Inhibited uptake and accelerated efflux of Am were attempted with the pneumophilic amphiphilics chlorimipramine, chlorphentermine, chlorpromazine, verapamil and with the main metabolite of Am: desethylamiodarone (60 and/or 240 microM; n = 3-4 lungs each). Lung extracted Am extensively during uptake. The amount of Am accumulated at 20 min (inflowing concentration: 30 microM) averaged 1307 +/- 109 (S.E.) nmol/g, corresponding to a tissue to medium ratio of 43.3 +/- 1.6. Spontaneous efflux of Am was incomplete. At 40 min, 862 +/- 105 nmol of Am remained bound per g of lung, suggesting sequestration of Am in a slowly effluxable pool in which calculations show that more than 50% of the drug will ultimately persist. Uptake and efflux rates obey biexponential kinetics, indicating storage into two pools. Uptake rate and the amount of Am accumulated in lung at 20 min increased in proportion to inflowing concentration up to 60 microM. At 120 microM the increase was less. Neither amphiphilic was capable of inhibiting Am uptake, whereas only chlorphentermine significantly accelerated Am efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2366186&dopt=Abstract

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