Maximum concentration in plasma

Rectal bioavailability and pharmacokinetics. Serenoa repens extract, administered rectally to 12 healthy male volunteers at a dose of 640 mg/person, produced the mean maximum concentration in plasma of nearly 2.60 (Xg/mL approx 3 hours after administration, with mean value for the area under the curve AUC 10 (Xg/hour/mL. The bioavailability and pharmacokinetic profile were similar to those observed after oral administration. T j occurred approx 1 hour later, and plasma concentration 8 hours after drug administration was still quantified. The drug tolerability was good, and no adverse effect was observed ". Serenoa repens capsules, administered orally at a dose of 160 mg four times daily or rectally 640 mg daily for 30 days to 60 patients with BPH, produced no significant differences in diminu-... 

Simultaneous Absorption and Elimination in Plasma. The ty e-concen-tration curves for the absorption and elimination of [ C]labeled parathion, carbaryl, and thiodicarb equivalents in plasma of adult rats are giv in Figure 8 and the pharmacokinetic constants in Table III. The [ C]equivalents were found in blood shortly after the application of the dose and reached maximum concentrations in plasma in 2.5 to 12 hr. Carbaryl and paraty on [ C]equivalents were eliminated during the study, while [ C]thiodicarb equivalents... 

Structural Physicochemical Biochemical Pharmacokinetic Molecular weight, ionization, polarity, lipophilicity/hydrophilicity, shape, reactivity, polar surface area, H-bonding Solubility, dissolution rate, permeability, chemical stability Protein/tissue/cell binding, metabolism, receptor mediated transport (influx and efflux) Bioavailability, half-life, clearance, drug-drug interactions, toxicity, maximum concentrations in plasma... 

Approximately one hundred studies have been published to date on the bioavailability and pharmacokinetics of individual polyphenols following a single dose of pure compound, plant extract or whole food/beverage to healthy volunteers. We recently reviewed the pharmacokinetic data available for each class to estimate average pharmacokinetic parameters including the maximum concentration in plasma (Qnax)> Tmax> the area under the plasma concentration versus time curve (Al/Q, ehmination half-life (Ti/2) and percent of dose excreted in urine (Manach and Donovan 2004). Here, we present a summary of that data... 

Exposure through inhalation As most of the quantity of the cyclic siloxanes evaporate shortly after application of the PCPs or volatilize from electronics, adhesives and sealants, polishes and surface cleaners, etc., the main pathway of exposure is through inhalation. Plotzke et al. [286] studied the inhalation exposure to D4 by exposing rats to C-DA. Using liquid scintillation counting, it was determined that the retention of inhaled D4 in the body of the rats was 5-6%. The radioactivity reached maximum concentrations in the fat 24 h after exposure, but in the plasma and other tissues (except for fat) in only 3 h. The fat tissue acted as a depot because the elimination of the radioactivity from it was slower than from other tissues. 

In summary, our bioavailability study provided for fhe firsf time data for fhe shorf-ferm bioavailability of ot-tocopherol solubilizate in comparison to regular fat-soluble preparations. Our results pointed to a higher short-term bioavailability of vitamin E in micelles versus fat-soluble forms of fhis vifamin in healthy adult volunteers both with regard to AUCs and with regard to maximum increases in plasma vitamin concentrations. 

In dogs, absorption following oral administration tends to be poor. At similar oral doses, peak serum levels are lower and plasma levels are less persistent than those observed for methicillin. Following intramuscular administration, however, maximum concentrations in serum are reached within 30 min. In contrast to methicillin, liver is the main excretory pathway for nafcillin. Like most other penicillins, nafcillin undergoes biotransformation to a small extent. Parent compound and its metabolites are excreted in bile and urine. Concentrations of nafcillin in tissues tend to be higher and more persistent following parenteral administration than was the case for methicillin, obviously due to enterohepatic recirculation. 

The persistence of flumequine residues in eel plasma and tissues was also determined for a 44 day period following a single intramuscular injection (168). The time to reach maximum concentrations of flumequine in tissues (48-192 h) was comparable to that in plasma (96 h). Mean maximum concentrations in tissues ranged from 725 ppb in bone to 121,000 ppb in fat. These concentrations declined with time in all tissues to reach, 44 days after administration, the values of 769, 427, 238, 213, 197, 153, 89, and 85 ppb in liver, fat, muscle, plasma, spleen, skin, bone, and kidney, respectively. 

Absorption of fenbendazole is slow in ruminants but more rapid in monogastric animals. Maximum concentrations in blood are achieved at about 8 h in rats and rabbits, 24 h in dogs, and 2-3 days in sheep. Elimination of fenbendazole is predominantly by the fecal route. The metabolic pathway of fenbendazole is similar in rats, rabbits, dogs, sheep, cattle, goats, and chickens. It is rapidly metabolized to fenbendazole sulfoxide (oxfendazole), fenbendazole sulfone, fenbendazole 2-aminosulfone, and other minor metabolites detected in plasma. 

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed [33] and validated for the determination of donepezil in human plasma samples. Diphenhydramine was used as the IS. The collision-induced transition m/z 380 > 91 was used to analyze donepezil in selected reaction monitoring mode. The signal intensity of the m/z 380 —> 91 transition was found to relate linearly with donepezil concentrations in plasma from 0.1 to 20.0 ng/ml. The lower limit of quantification of the LC/MS/MS method was 0.1 ng/ml. The intra- and inter-day precisions were below 10.2% and the accuracy was between 2.3% and +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 5 mg donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to fit the donepezil plasma concentration-time curve. Maximum plasma concentration was... 

For most flavonoids, the maximum concentration in human plasma occurs 1-6 hours after ingestion with an elimination half-life (t1/2) from 1 to 28 hours.15-21 Therefore, flavonoids can accumulate in the circulation and in tissues with frequently repeated intakes. Plasma quercetin in free-living subjects, measured after overnight fast, is typically 50-80 nmol/L, though smaller values are observed following a low-flavonoid diet.15 Conversely, supplementation with 500 mg/d rutin for 6 weeks increased plasma quercetin to 165 nmol/L22 and to 0.63 and 1.5 prnol/L following supplementation with 80 mg and >1 g quercetin equivalents daily for 7 and 28 days, respectively.23-24... 

The pharmacokinetic profile of HL6-7 was similar to that of HI-6. The mean absorption half-time of HL6-7 was about 14 min after intramuscular administration. Maximum HL6-7 concentration in plasma was reached after 30 min and the half-time of elimination was about 45 min (Eyer et al, 1992). 

The biological hulMile of pralidoxime chloride in humans is about 2 hours, and its cITcctiveness is a function of its concentration in plasma, which reaches a maximum 2 to 3 hours after oral administration,... 

The direct application of Eq. (23.25) to in vivo PD data assumes that drug concentrations in plasma and the biophase are in rapid equilibrium and directly proportional. Furthermore, maximum or peak effects are assumed to occur at peak drug concentrations (i.e., lack of hysteresis in concentration-effect curves). However, the operational model may be included also in indirect response models that characterize the temporal displacement between concentration and effect in mechanistic terms (26). 

The dye removed from the plasma by the hepatic cells may be metabolized before excretion into bile as in the case of BSP, or it may be excreted without metabolism, as in the case of rose bengal and indocyanine green. When BSP is injected intravenously there is a time lapse before it reaches maximum concentration in the bile (C2, C7, C8, C34, RIO). This has been attributed to storage of BSP in the liver and possibly to its conjugation, although some of the delay is due to the dead space of the biliary system in analogy to the delay time of the urinary tract (C18, M23). 

If Tl is applied intravenously, it is rapidly absorbed by tissue cells. Within a few minutes only 39% remains in the plasma. Maximum concentrations in muscles are reached after 4-8 h, and finally in the brain after 24 h (Rauws, 1974). 

Peak and trough concentrations The maximum and minimum drug concentrations—in plasma or blood—measured during cycles of repeated dosing... 

The pharmacokinetios of interferon is not well understood. Maximum levels in blood after intramuscular injection was obtained in 5 to 8 hours. Interferon does not penetrate well into cerebrospinal fluid (CSF). Oral administration of interferon does not indicate a detectable serum level, and as such, oral administration is olinioally ineffective. After intramuscular or suboutaneous injection, drug concentration in plasma is dose related. Clinioal use of interferon is limited to topioal administration (nasal sprays) for prophylaxis and treatment of rhinovirus infections. Adverse reaotions and toxioity include influenza-like syndrome of fever, ohills, headaohe, myalgias, nausea, vomiting, diarrhea, bone marrow suppression, mental confusion, and behavioral changes. Intranasal administration produoes mucosal friability, ulceration, and dryness. 

The nurse must also know the dmg s onset of action, peak action, and duration of action. As you ll recall from the previous chapter, onset is the time period when the dmg reaches the minimally effective concentration in the plasma. The peak action is when the dmg reaches the maximum concentration in the plasma. The duration is the length of time the therapeutic action will last. 

When fi-lactams are formulated as aqueous solutions for parenteral (intramuscular or subcutaneous) use, they are rapidly absorbed to achieve maximum concentrations in 0.25-1 h. In many cases, therefore, the plasma concentration-time profile is very similar for intravenous and intramuscular routes. 

Fig. 3.1 Bioequivalence of two drugs. Reference drug A caused a somewhat higher maximum concentration in blood plasma pg/ml, AUC=125 pg h/ml), but drug B satisfies the bio-...

Cmax Maximum (peak) drug concentration in plasma. The C ax often correlates widi toxicity and/or efficacy. 

Following single dermal applications of 10 mg/kg of radiolabeled methyl parathion to pregnant rats, methyl parathion was found to be widely distributed to all major tissues and organs. Concentrations were highest in plasma and kidney, maximum levels measured 2 hours postapplication. Peak levels in liver, brain, fetus, and placenta, were measured 2 to 10 hours later, at which times the highest concentration of methyl parathion was in the fetus (Abu-Quare et al. 2000). 

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