Elimination half-live

The pharmacokinetics of azacitidine shows that it is rapidly absorbed after s.c. administration with the peak plasma concentration occurring after 0.5 h. The bioavailability of s.c. azacitidine relative to i.v. azacitidine is approximately 89%. Urinary excretion is the primary route of elimination of azacitidine and its metabolites. The mean elimination half-lives are about 4 h, regardless of i.v. or s.c. administration. 

Oxicams, e.g. piroxicam, tenoxicam, meloxicam and lornoxicam are non-specific inhibitors of COX. Like diclofenac, meloxicam inhibits COX-2 ten times more potently than COX-1. This property can be exploited clinically with doses up to 7.5 mg per day, but at higher doses COX-1-inhibition becomes clinically relevant. Since the dose of meloxicam commonly used is 15 mg daily, this agent cannot be regarded as a COX-2-selective NS AID and considerable caution needs to be exercised when making comparisons between the actions of meloxicam and those of other conventional NSAIDs. The average daily dose in anti-rheumatic therapy is 20 mg for piroxicam and tenoxicam, 7.5-15 mg for meloxicam and 12-16 mg for lornoxicam. Oxicams have long elimination half-lives (lornoxicam 3-5 h, meloxicam - 20 h, piroxicam 40 h and tenoxicam 70 h). 

Renal excretion is the most important endosulfan elimination route in humans and animals. Biliary excretion has also been demonstrated to be important in animals. Estimated elimination half-lives ranged between approximately 1 and 7 days in adult humans and animals. Endosulfan can also be eliminated via the breast milk in lactating women and animals, although this is probably a relatively minor elimination route. No studies were located regarding known or suspected differences between children and adults with respect to endosulfan excretion. 

Pharmacokinetic parameters of the newer antidepressants are shown in Table 35— 5.9,29 Several antidepressants are not very highly protein bound, and the most notable of these is venlafaxine. The elimination half-lives of nefazodone and... 

TA Hicks, B Patel, LL Augsburger, R Shangraw, L Lesko, V Shah, D Young. The effect of relative magnitudes of absorption and elimination half-lives on the decision of Cmax-based bioequivalence (abstr). American Association of Pharmaceutical Scientists, 8th Annual Meeting, Orlando, FL, November 1993. 

The elimination of other compounds in which sulfation (e.g., chloramphenicol) is not an alternative pathway are subject to prolonged elimination half-lives... 

Prasad et al. [126] developed and used a sensitive and specific spectropho tome trie method for the estimation of primaquine to study the plasma kinetics of primaquine in Rhesus monkeys. It was observed that the drug completely disappeared from the plasma in 24 h after a single oral dose. Its concentration in the plasma reached a peak at 2 h of administration. The mean absorption and elimination half-lives were 0.36 0.08 and 3.44 0.37 h, respectively. 

Yoshimura et al. [132] studied the pharmacokinetics of primaquine in calves of 180—300 kg live weight. The drug was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously or subcutaneously and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high performance liquid chromatography. The extrapolated concentration of primaquine at zero time after the intravenous administration was 0.5 0.48 pg/mL which decreased with an elimination half-life of 0.16 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.5 0.08 pg/mL at 1.67 0.15 h after intravenous administration. The corresponding value was 0.47 0.07 pg/mL at 5.05 1.2 h after subcutaneous administration. The elimination half-lives of carboxyprimaquine after intravenous and subcutaneous administration were 15.06 0.99 h and 12.26 3.6 h, respectively. 

Biota elimination half-lives t,/2 = 2 d from Oyster for naphthalenes, t1/2 = 2.0 d from clam Macoma balthica quoted, Meador et al. 1995). 

Biota elimination half-lives t,/2 = 2.0 d from rainbow trout, t,/2 = 26.2 d from clam Mya arenaria, t,/2 = 6.3-13.3 d from mussel Mytilus edulis t,/2 = 9.2 d from Oyster, t,/2 = 1.2 d from shrimp, t,/2 = 5.7 d from polychaete Nereis virens, t,/2 = 8.0 d from clam Mercenario mercenaria (quoted, Meador et al. 1995). 

Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, hallucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepani, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

Individual metabolism cages are recommended for collecting urine and feces in oral dosing studies. Excreta should be collected for at least 5 elimination half-lives of the test substance. When urine concentrations will be used to determine elimination rates, sampling times should be less than one elimination half-life (taken directly from the bladder in IV studies) otherwise, samples should be taken at equal time intervals. 

The uptake and elimination half-lives of 176 and 169 min and 27 and 29 min were similar to each other and to half-lives obtained using mussels maintained in the laboratory. Half-lives in the longer term laboratory culture experiments (Table IV) were similar to each other. Similarly, the mantle cavity and body water constants gave no indication of stress (Table II). Mussels used in these experiments were selected by size (ca. 6 g viscera fresh weight) and variability could be reduced by adoption of more objective criteria. Instant Ocean culture does not directly effect antipyrine disposition and laboratory conditions are suitable for maintenance of animals for at least short times. 

After either oral or intravenous administration of ondansetron to laboratory animals the elimination of the drug is rapid. The short elimination half-lives t ji Table 7.7) reflect the high plasma clearance (CLp) in these species. Renal clearance (CLr) is below glomerular filtration rate, indicating that the major component of systemic clearance is metabolism. Ondansetron is rapidly absorbed after oral administration, peak concentrations in plasma being achieved within 40 min of dosing. However, the oral bioavailability is low. The similarity between concentrations of total drug-related material in plasma after oral and intravenous doses indicates that the low... 

Therefore the yield of N -SDM formed and excreted per min. (excretion rate) is higher in man than in pigs resulting in man in shorter elimination half-lives to 7 h vs. 9 to 14 h for pigs). The... 

The time required to reach steady-state accumulation during multiple constant dosing depends on the rate of elimination. As a rule of thumb, a plateau is reached after approximately three elimination half-lives (ti/2). 

The range of elimination half-lives for different benzodiazepines or their active metabolites is represented by the shaded areas (B). Substances with a short half-life that are not converted to active metabolites can be used for induction or maintenance of sleep (light blue area in B). Substances with a long half-life are preferable for long-term anxiolytic treatment (light green area)... 

Hattis et al. (1987) examined the variability in key pharmacokinetic parameters (elimination half-lives (Ty ), area under the curve (AUC), and peak concentration (C ax) in blood) in healthy adults based on 101 data sets for 49 specific chemicals (mostly drugs). For the median chemical, a 10-fold difference in these parameters would correspond to 7-9 standard deviations in populations of normal healthy adults. For one relatively lipophilic chemical, a 10-fold difference would correspond to only about 2.5 standard deviations in the population. The authors remarked that the parameters studied are only components of the overall susceptibility to toxic substances and did not include contributions from variability in exposure- and response-determining parameters. The study also implicitly excluded most human interindividual variability from age and diseases. When these other sources of variability are included, it is likely that a 10-fold difference will correspond to fewer standard deviations in the overall population and thus a greater number of people at risk of toxicity. 

The systemic clearance of lepirudin is proportional to the glomerular filtration rate or creatinine clearance. Dose adjustment based on creatinine clearance is recommended (see Administration and Dosage). In patients with marked renal insufficiency (creatinine clearance less than 15 mL/min) and on hemodialysis, elimination half-lives are prolonged 2 days or less. 

Pharmacokinetics The elimination half-lives of these drugs range from 4 to 8 hours. Elimination is primarily via hepatic metabolism. Plasma concentrations of alosetron are 30% to 50% lower and less variable in men compared with women given the same dose. Plasma protein binding is 82% for alosetron, 65% for granisetron and 70% to 76% for ondansetron. The terminal elimination half-life of alosetron is approximately 1.5 hours. 

Mirtazapine- Mirtazapine is rapidly and completely absorbed following oral administration and has a half-life of approximately 20 to 40 hours, with females of all ages exhibiting significantly longer elimination half-lives than males (37 vs 26 hours). Steady-state plasma levels of mirtazapine are attained within 5... 

Pharmacokinetics After IM or subcutaneous injection, the apparent fraction of dose absorbed was greater than 89%. The mean elimination half-life after IV administration was 38 minutes. The mean elimination half-lives for IM and subcutaneous dosing were 2.9 and 5.9 hours, respectively. Peak plasma concentrations occurred approximately 4 hours after IM dosing and 7 hours after subcutaneous dosing. 

Excretion - Following oral administration of an 80 mg dose of C-isotretinoin as a liquid suspension, C-activity in blood declined with a half-life of 90 hours. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%). After a single 80 mg oral dose of isotretinoin to 74 healthy adult subjects underfed conditions, the mean elimination half-lives of isotretinoin and 4-oxo-isotretinoin were approximately 21 and 24 hours, respectively. After single and multiple doses, the observed accumulation ratios of isotretinoin ranged from 0.9 to 5.43 in patients with cystic acne. 

What the body does to the drugs which enter the system may be referred to as pharmacokinetics. During a drug overdose and subsequent intoxication, the various parameters for pharmacokinetics are altered, and these will include changes in elimination half-lives, protein binding, saturation kinetics and excretion. These deviations from the normal pharmacokinetics may be referred to as toxicokinetics. 

Agents in this class are omeprazole, lansoprazole, pantoprazole and rabeprazole. Esomeprazole is the S-enantiomer of omeprazole. After ingestion of gastric acid resistant formulations they are rapidly and more or less completely absorbed. Bioavailability may be reduced if administered with food or antacids. Elimination is via metabolism in the liver and the renal excretion of inactive metabolites. The elimination half-live is very variable, however, as explained above, not related to the duration of action. 

Some penicillins cannot be given orally as their beta-lactam ring is hydrolyzed and inactivated in the stomach by gastric acid. In general intramuscular injections are painful and therefore not advised. The pharmacokinetic behavior of penicillins is further characterized by short elimination half-lives. Renal elimination is prominent. 

The macrolides are orally absorbed but they are acid-labile. They therefore need to be administered in acid-resistant capsules or as acid-resistant esters. The macrolides are widely distributed into all fluids except the CNS. Protein binding is about 90%. They are eliminated via biliary excretion with extensive enterohepatic circulation. Elimination half-lives vary from 1.4 h for erythromycin to 40-60 h for azithromycin. 

---