Talk:Bioavailability

Ecological Bioavailability

Can we have a discussion about bioavailability in the context of ecology? For instance, what it means for a particular molecule to be bioavailable to a microbe. I think this is an important definition of bioavailability, though, I'm not the one to define it. Any takers? --Jen Duane 08:28, 15 November 2005 (UTC)

Environmental Bioavailability

I think this article should be split into

1. Bioavailability from a biological/ecological viewpoint
   
2. Bioavailability from an environmental viewpoint
   
3. Bioavailability from the point of view of human health and nutrition

"Bioavailability has been defined differently by various disciplines, which has confounded use of the term. For this reason, the NRC (-I assume US National Research Council-) report contains no explicit definition of bioavailability"

Ehlers, L. J.; Luthy, R. G. Contaminant bioavailability in soil and sediment. Environ. Sci. Technol. 2003, 37, 295A–302A. The same article defines bioavailability in this way: "Bioavailability refers to the extent to which humans and ecological receptors are exposed to contaminants [in the environment]"

Another article sees bioavailability as "[...] a descriptor for the rate and extent of biodegradation [...]" and gives example of definition that have been proposed earlier for the field of environmental pollution. Semple, K.T.; Doick, K.J.; Wick, L.Y.; Harms, H. Microbial interactions with organic contaminants in soil: Definitions, processes and measurement. Env. Pol. 2003, 150, 166-176. Riennn (talk) 13:44, 28 September 2009 (UTC)

Explanation please...

In the formula for Absolute Availability: $F={\frac {[AUC]_{po}*dose_{IV}}{[AUC]_{IV}*dose_{po}}}$, what does the 'po' mean? I guess it is related to 'extra-vascular', but it is not obvious. What does the 'dose-corrected AUC' mean? — Preceding unsigned comment added by Duncan.france (talk • contribs) 22:45, 18 March 2006 (UTC)

Hi Duncan.france, "po" is conventional medical abbreviation for per os (by mouth). It made more sense when I originally wrote this article, because (to keep things simple) I only referred to absolute bioavailability of orally-administered drugs. But since people have added comments about other extravascular routes, I've now modified the text to try to explain. Dose corrected AUC means that doses of the drug given IV or non-IV can be different, so the formula for calculating F takes this into account. Hope that helps – let me know if it needs to be clarified further in the text. -Techelf 09:14, 20 March 2006 (UTC)

the formula is wrong... see http://www.chm.davidson.edu/erstevens/AUC/AUC.html — Preceding unsigned comment added by 138.37.111.164 (talk • contribs) 10:45, 4 April 2006 (UTC)

The page you cite actually just contains another way of expressing the same formula (think about it)... -Techelf 10:56, 4 April 2006 (UTC)

Are you sure that bioavailibility means "amount observed in blood relative to amount administered"? I've seen several definitions and some of them are more of the form "amount delivered to target tissue relative to amount administered". With the first definition, if you delivered a CNS drug intrathecally, you would have a bioavaibility actually less than the effectice dose to the target tissue which seems somewhat strange to me. 69.37.255.177 16:32, 17 June 2007 (UTC)GMM

Grammatical errors

I noticed multiple grammatical errors while reading this article. I would correct them but I'm on an iPhone and quite limited at this moment. To find an example, text search for "such that". Don't remember the context exactly. Sporky023 (talk) 23:24, 18 November 2010 (UTC)

Please explain

Kindly explain how come theophylline has a bioavailability greater than 100%. Ashu 15:52, 12 December 2011 (UTC)

Hi Ashu! To quote the note about theophylline: ‘If administered as an oral solution F is 111%, since the drug is completely absorbed and first-past metabolism in the lung after iv administration is bypassed.’ Might be confusing. Let's put it that way: From an orally administered solution 100% is absorbed → liver → systemic circulation (heart/body). Now for the tricky part: If administered intravenously the drug enters via the pulmonary circulation and is metabolized in the lungs before going to the heart and the systemic circulation. In other words if we administer the same dose orally and intravenously, the concentrations (and therefore the AUC) will be higher after the oral dose because we don't get the metabolization from the lungs. Therefore F>100%. Very (very) rare, but possible. Alfie↑↓© 21:31, 12 December 2011 (UTC)

Hi Alfie66, i have got you partly but in your explaination you are assuming that the degree of metabolization in lungs is greater than in the liver. Right?

I have another theory.

See, the reference to the bioavailability of theophylline being around 111% is actually for the sustained-release tablets manufactured by a certain company. Now, it may be possible that, in case of i.v. administration since the dose is given at once so theophylline is metabolized equally quickly unlike in the tablet form in which only smaller amounts enter the circulation "continually" yet over a longer period of time. Thus, though plasma concentration of theophylline in case of i.v. may be higher but in sustained-released form it is for a longer time ergo with a larger AUC.

What is confusing me now is the assumption that AUC(sustained-release) "can" be greater than AUC(i.v.) -Ashu 13:50, 13 December 2011 (UTC) — Preceding unsigned comment added by Ashu1990 (talk • contribs)

Plasmalevel-curves after extravascluar adminstration of various formulations
1 immediate release (IR)
2 delayed release (DR)
3 controlled release (CR)
4 Transdermal system

Hi Ashu! Concerning your first sentence: yes. Actually we don't know. The problem in comparing AUCs (from doses administered on different occasions) comes from a main assumption, namely that the clearance stays the same. This is a major obstacle in bioequivalence of highly variable drugs. The formulations may have little variability, but the large variability in all the elimination processes involved may require large numbers of volunteers in order to get a statistically meaningfull result. Theophylline is not a highly variable drug, but the 111% may have been pure chance as well. On the other hand if you search the literature you will find some small studies, and the overall AUC-ratio is >100%. The PK-community actually refers to theophylline as a model drug for first-pass metabolization in the lungs. The only way to find it really out is as following: Administer a solution orally (= no influence of a formulation) and simultaneously an intravenous dose of the same drug which is labelled by a stable isotope (e.g. ¹³C). After analyzing samples (and separating isomers by mass spectrometry) we know the ‘true’ AUCs (without requiring the assumption of equal clearances). Unfortunatelly this is rarely done, mainly because it's quite cumbersome to get regulatory clearance of the labelled i.v. formulation (must comply with GMP rules).
See also: Lappin G, Rowland M, Garner RC (2006). "The use of isotopes in the determination of absolute bioavailability of drugs in humans". Expert Opin Drug Metab Toxicol. 2 (3): 419–27. doi:10.1517/17425255.2.3.419. PMID 16863443. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
BTW, in linear pharmacokinetics AUCs are identical regardless how fast (or slow) the input rate is. See the little plot. Only if some enzyme(s) get saturated (can't metabolize high doses as fast as low doses) or are induced (the drug itself stimulates the production of the enzyme) AUCs might differ. But you see this mainly if comparing a wide dose range and/or in steady state (after multiple doses, especially if accumulation occurs). Hope that helps.
P.S.: Please sign your posts with for tildes (~~~~) – the software will add your username and a timestamp. THX. Alfie↑↓© 18:14, 15 December 2011 (UTC)

Oops, just realized that the stable-isotope story (including the same reference I gave) is already part of the article… Alfie↑↓© 18:25, 15 December 2011 (UTC)

Clarification

In the article bioavailability has been called both 'rate' and 'extent'. By definition and use, bioavailabilty is a fraction and thus a dimensionless quantity. Thus, it cannot be a 'rate'.Ashu 18:08, 21 January 2012 (UTC) — Preceding unsigned comment added by Ashu1990 (talk • contribs)

Hi Ashu! You are right; pharmacologists mean by bioavailability the ratio of AUCs (dimensionless f or if given as a percentage denoted by F). Rate of bioavailability is only given in connection with bioequivalence testing following FDA's (and all regulatory agencies worldwide) terminology. See CFR Title 21, Volume 5, Part 320.23 (a)(1): The in vivo bioavailability of a drug product is measured if the product's rate and extent of absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, urinary excretion rates, or pharmacological effects, do not indicate a significant difference from the reference material's rate and extent of absorption. This definition is clumsy but we have to live with it (legally binding). Depending on the formulation (given in product-specific guidances) generally the ratio of C_max-values or the ratio of partial AUCs (AUC from the time point of administration to the time point of the median t_max of the population under the reference treatment) has to be assessed. This ratio is also dimensionless. Alfie↑↓© 14:04, 23 January 2012 (UTC)

Broaden the article?

Bioavailability is an important concept in nutrition. "Mineral X in ... food, but it is not bioavailable because ". That kind of discussion. One idea is to have two articles, Bioavailability(pharmaceuticals) and Bioavailability(nutrition). --Smokefoot (talk) 20:11, 25 August 2023 (UTC)