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1.
Chemotherapy ; 48(5): 217-23, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12476037

ABSTRACT

BACKGROUND: This two-way, randomized, single-dose, crossover study determined the pharmacokinetics and absolute oral bioavailability of telithromycin in young and elderly healthy subjects. METHODS: Twelve young (18-40 years) and 12 elderly (>65 years and

Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Ketolides , Macrolides , Administration, Oral , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/blood , Area Under Curve , Biological Availability , Cross-Over Studies , Female , Half-Life , Humans , Injections, Intravenous , Male , Time Factors
2.
Toxicology ; 137(2): 117-27, 1999 Sep 20.
Article in English | MEDLINE | ID: mdl-10521148

ABSTRACT

To study the influence of the interval between digoxin intake and digoxin-specific antigen binding fragment (DSFab) administration, we developed a rat kinetic model. 3H-digoxin (0.77 nmol/kg) was injected by intravenous route and DSFab was injected at different times (12, 30 or 60 min) corresponding to different levels of 3H-digoxin distribution (50, 83 and 100%). The effect of increasing the molar DSFab/3H-digoxin ratio from 1 to 5 was also investigated. To evaluate DSFab effect on the 3H-digoxin pharmacokinetics, we also investigated the pharmacokinetics of the 125I-DSFab and DSFab-3H-digoxin complex. 3H-digoxin and DSFab-3H-digoxin complex pharmacokinetics showed that DSFab altered immunoreactive 3H-digoxin pharmacokinetics. In redistribution studies performed 12, 30 or 60 min after 3H-digoxin injection, DSFab bound immunoreactive 3H-digoxin including native 3H-digoxin and active metabolites of 3H-digoxin. This binding induced a redistribution process of immunoreactive 3H-digoxin in the DSFab distribution compartment and was evaluated by the redistribution fraction (F(R)). F(R) was 23% lower at 60 min than at 12 and 30 min, and by increasing the DSFab/3H-digoxin ratio from 1 to 5, F(R) increased by 60%. In conclusion, the longer the time interval between digoxin intake and DSFab administration, the lower the efficacy of the redistribution process. This effect could be reduced by increasing the DSFab dose.


Subject(s)
Antigens/metabolism , Cardiotonic Agents/pharmacokinetics , Digoxin/pharmacokinetics , Immunoglobulin Fab Fragments/metabolism , Animals , Antibody Specificity , Area Under Curve , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Half-Life , Male , Models, Biological , Rats , Rats, Sprague-Dawley , Time Factors , Tissue Distribution
3.
Int J Clin Pharmacol Ther ; 37(10): 503-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10543318

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the pharmacokinetics and the accumulation and stationarity of thiocolchicoside after repeated intramuscular administration. METHOD: The pharmacokinetics of thiocolchicoside were studied in 6 healthy male volunteers after one single dose and repeated intramuscular doses of 4 mg twice a day for seven days. Plasma and urine samples were assayed for thiocolchicoside levels by a radioimmunoassay (RIA) using a cross-reacting colchicine-specific polyclonal antibody. The pharmacokinetic parameters between the first and the last days were compared using Student's t-test. RESULTS: Thiocolchicoside pharmacokinetic parameters, calculated after the single dose using non-compartmental analysis, were in good agreement with those obtained in previous studies. Following the repeated-dose regimen, the terminal half-life was not significantly different (2.7 (0.3) h) from that predicted from a single-dose (2.8 (0.2) h). The accumulation ratio, based on the repeated-dose/single-dose ratio of AUCtau was approximately 1.25. A decrease of CLT/f was found between day 1 (24.1 (5.2) l/h) and day 7 (19.9 (3.4) l/h), suggesting that moderate time-related alterations occur in the pharmacokinetics of thiocolchicoside, which may be due to a change in its CL(NR) (CL(R) was constant) or to the extent of bioavailability, explained by enterohepatic recirculation. CONCLUSION: Serum thiocolchicoside concentrations accumulated to steady-state when the drug was given twice a day for seven days and the pharmacokinetics were modified. But no adjustments of dose or dosing interval were necessary because the accumulation did not lead to marked change in the plasma levels.


Subject(s)
Colchicine/analogs & derivatives , Absorption , Adult , Area Under Curve , Biological Availability , Colchicine/administration & dosage , Colchicine/adverse effects , Colchicine/pharmacokinetics , Colchicine/urine , Drug Administration Schedule , Half-Life , Humans , Injections, Intramuscular , Kinetics , Male , Radioimmunoassay
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