Biphasic elimination curve

There was a significant negative correlation between (log) admission urinary PCP level and self-reported time since last PCP use (r= -0.53, p<0.001). Visual inspection of a graph of these two variables suggested a possible biphasic elimination curve, with the initial phase having a half-life of 5 to 7 days, and the later phase a half-life of about 30 days. However, formal curve fitting of these data to standard pharmacokinetic models (using BMDP... 

In rats, excretion of lead was biphasic following intravenous administration, with half-lives of 21 hours for the fast phase and 280 hours for the slow phase (Morgan et al. 1977). Dogs excreted lead in three phases, with half-lives of 12, 184, and 4,951 days (Lloyd et al. 1975). The half-life of the terminal phase of a biphasic elimination curve for mice was 110 days (Keller and Doherty 1980a). 

Shih et al. (1994) injected rats subcutaneously with a single dose of 75]Hg/kg of sarin, cyclosarin, and soman, and measured excretion of the hydrolyzed metabolites and the alkylmethylphosphonic acids, including IMPA and corresponding MPAs. MPA was a major and common metabolite of the three compounds. Urinary excretion over the first 24 h accounted for approximately 90% of the administered doses of sarin and cyclosarin. Almost total recoveries of the given doses for sarin and cyclosarin in metabolite form were obtained from the urine. Urinary elimination was found to be rapid and the terminal elimination half-life of sarin metabolites in urine was 3.7h. Most of the administered dose of sarin was retrieved from the urine in a metabolite form after 2 days. The terminal elimination half-life of cyclosarin in urine was 9.9 h. Soman metabolite showed a biphasic elimination curve with terminal half-lives of 18.5 and 3.6 h. Soman was excreted at a slower rate, with a recovery of only 62%. The first phase of elimination of soman results from enzymatic hydrolysis of the inactive P( + ) isomers, and the slower phase is from the active P( - ) isomers (Benschop and De Jong, 1991). The elimination study in rats determined IMPA in blood up to 14 h after exposure, CHMPA up to 2 days, and PMPA up to at least 3 days. 

In calves and cows at high dose levels (100 SDM mg/kg), a biphasic elimination SDM plasma concentration-time curve was observed with a steady state plasma SCH2OH concentration resulting from the capacity limited hydroxylation of SDM into the latter. The drug concentrations in the milk reflected those in plasma. 

Laying-hens eliminate sulfadimidine rapidly by metabolic pathways including hydroxylation and acetylation. Following intravenous SDM administration, a biphasic elimination-time curve was noticed 10.2 + 3.3 H). Figure 8 shows the plasma disposition of SDM and its metabolites following an oral SDM bolus administration once daily of 100 mg/kg to a chicken. The percentage of N -SDM in plasma is the highest (Table I). Within 3 days of termination of the SDM therapy, plasma concentrations of SDM and its metabolites falls rapidly below the detection limit of the HPLC method (0.02 /ig/ml). 

A plasma calibration curve for ll-nor-A9-THC-9-carboxylic acid, 5a, is shown in Figure 9. There was reasonable linearity from 1.0-50 ng/ml plasma with detection limits of 0.5 ng or less per ml. Figure 10 presents similar data for a urine calibration curve. The method showed reasonable linearity between 2.0-100 ng/ ml urine. Figure 11 presents pharmacokinetic data. for plasma levels of a human volunteer, BS, over a 0.5 hour to 48 hour period comparing A9-THC and 11-nor acid levels after a dose of 5.0 mg of A9-THC by the intravenous route. Both parent compound and acid metabolite exhibited a biphasic elimination pattern although the levels of the acid did not fall as rapidly as parent compound. Elimination of the acid metabolite 5a in urine is shown in Figure 12. It is evident that urinary elimination proceeded rapidly as 80% of the total 11-nor-acid excreted was eliminated in the urine during... 

After oral administration the bioavailability varies widely with a maximum of some 60%. Tacrolimus can also be administered intravenously. Its concentration-time curve is biphasic. It is metabolized in the liver and is eliminated with a half-life varying from some 12 hours in patients to 20 hours in healthy subjects. 

The elimination of [i C]triethanolamine from the blood of mice administered 1.0 mg/kg bw intravenously showed first-order biphasic kinetics with a rapid (0.58-h half-life) and a slow phase (10.2-h half-life). The slow phase half-lives for elimination of triethanolamine in mice after dermal exposure to 1000 and 2000 mg/kg bw in acetone were 9.7 h and 18.6 h. Skin absorption rates (as blood concentration-time curves) after dermal application of aqueous and neat [I CJtriethanolamine to mouse skin (2000 mg/kg bw, enclosed by a glass ring) showed no significant change with the use of water as the vehicle (Waechter Rick, 1988, cited in Knaak et al, 1997). 

In Equation 17.22, the body is considered as a single homogeneous pool of body fluids as described above for digoxin. For most drugs, however, two or three distinct pools of distribution space appear to exist. This condition results in a time-dependent decrease in the measurable blood or plasma concentration, which reflects distribution into other bod pools independent of the body s ability to eliminate the drug. Figure 17.3 describes mean serum IFN-a concentrations after a 40-min intravenous infusion as well as after intramuscular and subcutaneous injections of the same dose. Note the logarithmic biphasic nature of the mean plasma concentration-time curve after the intravenous infusion. This biphasic nature represents both the distribution and elimination processes. 

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