Drug administration bioavailability

Bioavailability is the amount of drug in a formulation that is released and becomes available for absorption or the amount of the drug absorbed after oral administration compared to the amount absorbed after intravenous administration (bioavailability - 100%), judged from areas remaining under plasma drug concentration-time curves. 

Since 1999, when the Food and Drug Administration allowed the first health claim for soy-fortified foods in the USA, there has been a large increase in the sales of food products claiming to contain soy isoflavones. At the same time, over-the-counter supplements have become widely available. However, concerns have been raised about the real health benefits of such supplements in the absence of adequate information about bioavailability, pharmacokinetics and safety. To fill this gap, an extensive study on pure isoflavones and commercial soy isoflavone supplements has recently been carried out (Setchell et al, 2001). A selection of 31 commercially available supplements showed a wide variation in isoflavone composition and in the amount provided by one tablet. Furthermore, a lower isoflavone content, with respect to the claimed levels, has been observed in almost 50% of the analysed products. In one case, no isoflavones at all could be detected (Setchell et al, 2001). 

For most practical purposes, a first-order process may be deemed complete if it is 95% or more complete. Table 1 shows that five half-lives must elapse to reach this point. Thus the elimination of a drug from the body may be considered to be complete after five half-lives have elapsed (i.e., 97% completion). This principle becomes important, for example, in crossover bioavailability studies in which the subjects must be rested for sufficient time between each drug administration to ensure that washout is complete. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

J. Zha and L. Endrenyi, Variation of the peak concentration following single and repeated drug administration in investigations of bioavailability and bioequivalence, J. Biopharm. Stat., 7, 191 (1997). 

Karlsson, M. O., Bredberg, U., Bioavailability estimation by semi-simultaneous drug administration a Monte Carlo simulation study,... 

Fig. 18.7. Oral bioavailability of saquinavir with and without CFJ [42], Saquinavir (600 mg three capsules of Invirase, 200 mg each tablet) was administered to eight healthy male subjects (average body weight 76 kg) before and after consumption of two glasses (200 mL each) of CFJ at 15 and 45 min before drug administration. QMPRPIus was used to estimate human effective permeability (0.93 X 10-4 cm s 1), pure aqueous water...

CDER Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system Food and Drug Administration, 2000. 

The most significant drug-nutrient interactions result in reduced bioavailability and suboptimal pharmacologic effect (Table 58-4). Continuous feeding requires interruption for drug administration and medications... 

U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. 2000. 

Food and Drug Administration Guidance for Industry. Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations, March 2003. 

Absorption/Distribution - Lamotrigine is rapidly and completely absorbed after oral administration. Absolute bioavailability is 98%. Peak plasma concentrations occur anywhere from 1.4 to 4.8 hours following drug administration. Lamotrigine chewable/dispersible tablets were found to be equivalent, whether they were administered as dispersed in water, chewed and swallowed, or swallowed as whole, to lamotrigine compressed tablets in terms of rate and extent of absorption. 

Nitisinone is a reversibile inhibitor of 4-hydroxy-phenylpyruvate oxidase, an enzyme that plays a crucial role in the tyrosine catabolic pathway. Nitisinone prevents the accumulation of the toxic metabolites fumaryl acetoacetate, succinyl acetoacetate and succinyl acetone. Nitisinone is used for the treatment of hereditary tyrosinemia type 1. After oral administration bioavailability is 90% and peak levels are reached at 2.5 hours after dosing. The drug is eliminated mainly in the urine but some CYP3A4-mediated metabolism seems to occur. The elimination half-life is 45 hours. Blood dyscrasias are frequently occurring side effects as are eye problems like conjunctivitis, corneal opacity and keratitis. Exfoliative dermatitis, erythematous rash and pruritus... 

The standard pharmacokinetic parameters of the compound such as a half-life or bioavailability cannot be reliably calculated, because the concentrations in plasma are below lOpg/mL. As analogously expected from the results on the shift in keto-alcohol equilibrium of 16,16-difluoro-PGE2, it is rapidly metabolized by C-15 reduction mediated by the ubiquitously expressed carbonyl reductase. The metabolism followed by jS-oxidation and co-oxidation forms a mixture of a and fi epimers at the 15-hydroxy moiety as a sole measurable metabolite [46], In 2006, the US Food and Drug Administration approved the drug application for an oral treatment of chronic idiopathic constipation in adults, estimating that 4-5 million Americans are affected. Lubiprostone has also completed a phase II trial in constipation-predominant irritable bowel syndrome, and has been further evaluated for other bowel dysfunctions. 

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-... 

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