Chronopharmacological study of interferon-alpha in mice. 1997

S Koyanagi, and S Ohdo, and E Yukawa, and S Higuchi
Department of Clinical Pharmacokinetics, Kyushu University, Fukuoka, Japan.

The influence of dosing time on the pharmacological effects (fever and antiviral activity) and the pharmacokinetics of interferon-alpha (IFN-alpha) was investigated in ICR male mice under light-dark (12:12) cycle. There was a significant circadian rhythm in rectal temperature, as an index of fever, at 0.5 hr after IFN-alpha (10.0 MIU/kg i.v.) injection. The rhythmic pattern resembled overall the rhythm that occurs in the nondrugged state. However, the percent change from basal level of rectal temperature varied according to the dosing time. The rhythmicity corresponded to the dosing time-dependent difference of PGE2 levels in thalamus after IFN-alpha injection, but it did not correspond to that of plasma IFN-alpha concentrations. A significant dosing time-dependent difference was also demonstrated for 2'-5'oligoadenylate synthetase activities, as an index of antiviral activity, in plasma and liver at 24 hr after IFN-alpha injection. It was related to the rhythmicity in plasma IFN-alpha concentrations that was caused by the rhythmicity in clearance of IFN-alpha. The choice of the most appropriate time of day for drug administration may help to achieve rational chronotherapeutics of IFN-alpha in certain experimental and clinical situations.

UI MeSH Term Description Entries
D008297 Male Males
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D001831 Body Temperature The measure of the level of heat of a human or animal. Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015088 2',5'-Oligoadenylate Synthetase An enzyme that catalyzes the conversion of ATP into a series of (2'-5') linked oligoadenylates and pyrophosphate in the presence of double-stranded RNA. These oligonucleotides activate an endoribonuclease (RNase L) which cleaves single-stranded RNA. Interferons can act as inducers of these reactions. 2',5'-Oligoadenylate Polymerase,2-5A Synthetase,(2'-5')An Polymerase,2',5'-Oligo(A) Polymerase,2',5'-Oligo(A) Synthetase,2,5 Oligoadenylate Polymerase,2,5 Oligoadenylate Synthetase,ATP-(2'-5')oligo(A)adenylyltransferase,2',5' Oligoadenylate Polymerase,2',5' Oligoadenylate Synthetase,Oligoadenylate Polymerase, 2,5,Oligoadenylate Synthetase, 2,5,Polymerase, 2',5'-Oligoadenylate,Polymerase, 2,5 Oligoadenylate,Synthetase, 2',5'-Oligoadenylate,Synthetase, 2,5 Oligoadenylate
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D016898 Interferon-alpha One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways. Interferon Alfa,Interferon, Leukocyte,Interferon, Lymphoblast,alpha-Interferon,IFN-alpha D,IFN-alpha5,Interferon alpha-1,Interferon alpha-17,Interferon alpha-4,Interferon alpha-5,Interferon alpha-7,Interferon alpha-88,Interferon alpha-J,Interferon alpha-T,Interferon alpha4,Interferon alpha5,Interferon, Lymphoblastoid,Interferon, alpha,LeIF I,LeIF J,Leif D,IFN alpha D,IFN alpha5,Interferon alpha,Interferon alpha 1,Interferon alpha 17,Interferon alpha 4,Interferon alpha 5,Interferon alpha 7,Interferon alpha 88,Interferon alpha J,Interferon alpha T,Leukocyte Interferon,Lymphoblast Interferon,Lymphoblastoid Interferon,alpha Interferon
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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