Bibliographic Citation
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| Title | Distribution of primaquine in human blood: Drug-binding to alpha 1-glycoprotein |
| Creator/Author | Kennedy, E. ; Frischer, H. (Rush Univ., Chicago, IL (USA)) |
| Publication Date | 1990 Dec 01 |
| OSTI Identifier | OSTI ID: 6275948 |
| Other Number(s) | Journal ID: ISSN 0022-2143; CODEN: JLCMA |
| Resource Type | Journal Article |
| Resource Relation | Journal Name: Journal of Laboratory and Clinical Medicine; (USA); Journal Volume: 116:6 |
| Subject | 59 BASIC BIOLOGICAL SCIENCES; DRUGS; TISSUE DISTRIBUTION; GLYCOPROTEINS; BIOCHEMICAL REACTION KINETICS; BLOOD COUNT; CARBON 14 COMPOUNDS; ERYTHROCYTES; MEMBRANE TRANSPORT; TRACER TECHNIQUES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; DISTRIBUTION; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; MATERIALS; ORGANIC COMPOUNDS; PROTEINS; REACTION KINETICS |
| Description/Abstract | To clarify the distribution of the antimalarial primaquine in human blood, we measured the drug separately in the liquid, cellular, and ultrafiltrate phases. Washed red cells resuspended at a hematocrit of 0.4 were exposed to a submaximal therapeutic level of 250 ng/ml of carbon 14-labeled primaquine. The tracer was recovered quantitatively in separated plasma and red cells. Over 75% of the total labeled drug was found in red cells suspended in saline solution, but only 10% to 30% in red cells suspended in plasma. The plasma effect was not mediated by albumin. Studies with alpha 1-acid glycoprotein (AGP), tris(2-butoxyethyl)phosphate, an agent that displaces AGP-bound drugs, and cord blood known to have decreased AGP established that primaquine binds to physiologic amounts of the glycoprotein in plasma. Red cell primaquine concentration increased linearly as AGP level fell and as the free drug fraction rose. We suggest that clinical blood levels of primaquine include the red cell fraction or whole blood level because (1) erythrocytic primaquine is a sizable and highly variable component of the total drug in blood; (2) this component reflects directly the free drug in plasma, and inversely the extent of binding to AGP; (3) the amount of free primaquine may influence drug transport into specific tissues in vivo; and (4) fluctuations of AGP, an acute-phase reactant that increases greatly in patients with malaria and other infections, markedly affect the partition of primaquine in blood. Because AGP binds many basic drugs, unrecognized primaquine-drug interactions may exist. |
| Country of Publication | United States |
| Language | English |
| Format | Medium: X; Size: Pages: 871-878 |
| System Entry Date | 2008 Feb 07 |
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Last Updated: 11/19/2009