Plasma drug concentrations relative bioavailability

As discussed previously, the area under the plasma concentration versus time curve AUC) can be very useful in determining the bioavailability of a drug and other PK parameters. The ratio of bioavailability values (L1/L2) for a drug delivered by two different routes is called the relative bioavailability. The relative bioavailability can be determined from the dose D and D ) and AUC values AUCi and AUGp) of each route by the relationship... 

The relative bioavailability is the systemic availability of a drug from one drug product (A) compared to another drug product (B). Relative bioavailability can be calculated from Equations 5.6 and 5.7 using plasma concentration time data. 

Although the lipid solubility of sotalol is relatively low compared with other jS-blocking adrenoceptor drugs (28), oral bioavailability is deemed to be 1(X)%. Sotalol is absorbed somewhat slower than most other j8-blockers, with peak concentrations occuring within 2-3 hours (29). Although food may impair the absorption of sotalol (28), administration of either calcium carbonate or aluminum hydroxide antacids has little effect on absorption (30). After administration of a single 160 mg oral dose of sotalol, both enantiomers reached maximal plasma concentrations in approximately 3 hours (31) and, hence, did not exhibit stereoselective absorption. 

When plasma concentration data are utilized in the determination of the comparative (or relative) bioavailability, please note that peak plasma concentrations, (Cp)max and peak times (tmax) for the test and the reference products, in addition to the relative fraction of drug absorbed must also be compared. 

Combined morphine/naltrexone capsules are to be swallowed whole or the contents of the capsules sprinkled on apple sauce and the pellets in the capsules are not to be crushed, dissolved, or chewed. A pK study of combined morphine/naltrexone crushed vs. whole was done to compare the plasma concentrations and relative bioavailability of morphine, naltrexone, and the major naltrexone metabolite (6-P-naltrexol). Plasma morphine levels from crushed morphine/naltrexone capsules showed no extended-release properties. While concurrent administration of high-fat food decreased the rate and extent of morphine absorption from combined morphine/naltrexone, the total bioavailability or sequestration of naltrexone was not affected. An alcohol effects study examined the bioavailability of combined morphine/naltrexone when dosed under fasting conditions with 4%, 20% and 40% alcohol compared to water. The rate and extent of bioavailability and total exposure to morphine (AUC, C ) were not affected when the drug was adminis-tered concomitantly with either 4% or 20% alcohol, when compared to administration with water. When combined morphine/naltrexone was administered with 40% alcohol (240 mL over 15 minutes), the rate and extent of bioavailability (C ) doubled and the t was 5 hours earlier, when compared to administra-tion with water. The total systemic exposure to morphine (AUC) was not affected [9]. 

Oral administration of the peptide drug antide in a liquid dosage form showed no detectable concentration of the drug in plasma at all. When a thiolated chitosan was introduced into the formulation, however, an improved uptake of the drug was fotmd. The absolute and relative bioavailability of these formulations were calculated to be 1.1% and 3.2% increased, respectively [74]. 

Relative to an IV dose of 20 mg, the absolute oral bioavailability of metoclopramide is approximately 80%. Peak plasma concentrations occur at approximately 1 to 2 hours after a single oral dose. Similar time to peak is observed after individual doses at steady-state. The area under the drug... 

Oxybutynin has a relatively low oral bioavailability (6%) due to an extensive first-past presystemic metabolism after administration [194], Indeed, the absence of intact oxybutynin in urine suggests that the major elimination pathway of this drug is hepatic metabolism [195]. The compound is readily converted to its stable toxic metabolite, iV-desethyloxybutynin by cytochrome P450-mediated oxidation [196], Following oral administration of oxybutynin, peak plasma concentrations are reached within 1 h. The short half-life of this drug (less than 2 h), when administered as a conventional oral formulation, necessitates multiple 5 mg daily dosing [197],... 

Zalcitabine has a relatively long intracellular half-life of 10 hours (despite its elimination half-life of 2 hours) and high oral bioavailability (> 80%). However, plasma levels decrease by 25-39% when the drug is administered with food or antacids. Plasma protein binding is low (< 4%). Cerebrospinal fluid concentrations are approximately 20% of those in the plasma. 

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