# Bioavailability clarification

**URL:** <https://discourse.pumas.ai/t/bioavailability-clarification/440>\
**Category:** model-syntax\
**Created:** [November 28, 2020, 2:24pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440 "2020-11-28T14:24:58Z")\
**Posts on this page:** 5\
**Page:** 1

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**Author:** ![sai\_matcha](https://yyz2.discourse-cdn.com/flex030/user_avatar/discourse.pumas.ai/sai_matcha/32/297_2.png) [@sai\_matcha](https://discourse.pumas.ai/u/sai_matcha)\
**Post date:** [November 28, 2020, 2:24pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440/1 "2020-11-28T14:24:58Z")

</div>

I have two drugs which were administered in two different compartments. Both have different bioavailability values.  
can I use

```auto
bioav1 = (Depot1 = tvbio1, Central = 1-tvbio1)
bioav2 = (Depot2 = tvbio2, Central = 1-tvbio2)

```

If not how can i account for it?

I have one more doubt as well. I am little confused by looking “bioav” code.  
(itz given as Central = 1- tvbio)

If Bioavailbility of my drug is 75%, what can i give ?  
tvbio = 0.75 or tvbio = 0.25?

Thank you

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<div class="post-metadata">

**Author:** ![vijay](https://yyz2.discourse-cdn.com/flex030/user_avatar/discourse.pumas.ai/vijay/32/96_2.png) [@vijay](https://discourse.pumas.ai/u/vijay)\
**Post date:** [November 28, 2020, 3:01pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440/2 "2020-11-28T15:01:17Z")

</div>

hi Sai,

if you have two drugs, I am assuming that their `CL` and `Vc` or `Ka` parameters are different? They are given at the same time? Is there an interaction between the two drugs such that the PK of one impacts the other?

Your formulation above is incorrect. Assuming that both your drugs are going to the same Central compartment (at which point you cannot differentiate between the drugs), your `bioav` statement should be written like this

```auto
bioav = (Depot1 = tvbio1*exp(η[5]), Depot2 = tvbio2*exp(η[6]))

```

Here, since the assumption is that total bioavailability is `1`, you don’t have to specify explicitly that the `Central` is `1-tvbio`. It is implied.  
To your question about what value does `tvbio` take if your estimate of bioavailability if 75%. It should be 0.75 as you stated.

What are you trying to model? Perhaps some more detail can help address your question.

Best,  
Vijay

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<div class="post-metadata">

**Author:** ![sai\_matcha](https://yyz2.discourse-cdn.com/flex030/user_avatar/discourse.pumas.ai/sai_matcha/32/297_2.png) [@sai\_matcha](https://discourse.pumas.ai/u/sai_matcha)\
**Post date:** [November 28, 2020, 3:11pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440/3 "2020-11-28T15:11:17Z")

</div>

what i mentioned two drugs were , two different formulations of same drug.

1. when we give oral formulation drug is entering to central compartment from depot1 with absorption rate constant as KA.
2. prodrug was given in IV formulation. which is converting to drug and release to central compartment ( I am trying to use Depot 2 for prodrug administration, so when it is converted it will enter into central compartment with conversion rate constant as K23)
3. finally these two formulations release the same drug into Central compartment.

Thankyou

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<div class="post-metadata">

**Author:** ![vijay](https://yyz2.discourse-cdn.com/flex030/user_avatar/discourse.pumas.ai/vijay/32/96_2.png) [@vijay](https://discourse.pumas.ai/u/vijay)\
**Post date:** [November 28, 2020, 4:30pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440/4 "2020-11-28T16:30:20Z")

</div>

Since both drugs give the same final moiety, see if this works.  
You can play around with `d2` to figure out how the Prodrug is given. There are different ways to account for the overall contribution of both drugs. here I am just assuming that each route of administration has its own bioavailability.

```auto
using Pumas
using Plots
using Random

two_parallel_drugs = @model begin

  @param begin
    tvcl ∈ RealDomain(lower=0)
    tvv ∈ RealDomain(lower=0)
    tvka ∈ RealDomain(lower=0)
    tvbio1 ∈ RealDomain(lower=0)
    tvbio2 ∈ RealDomain(lower=0)
    Ω ∈ PDiagDomain(6)
    σ ∈ RealDomain(lower = 0.0001)
  end

  @random begin
    η ~ MvNormal(Ω)
  end

  @pre begin
    CL = tvcl*exp(η[1])
    Vc = tvv*exp(η[2])
    Ka = tvka*exp(η[3])
    bioav = (Depot = tvbio1*exp(η[5]), Central = tvbio2*exp(η[6]))
  end

  @dynamics Depots1Central1

  @derived begin
    conc := @. Central/Vc
    dv ~ @. Normal(conc, σ*abs(conc))
  end

end

d1 = DosageRegimen(100, cmt=1)
d2 = DosageRegimen(50, cmt=2, duration = 0.5)
dr = DosageRegimen(d1,d2)

pop = map(subj -> Subject(id = subj, events = dr), 1:10)

param = (
  tvcl = 5, tvv = 50, tvka = 0.8, tvbio1 = 0.8, tvbio2 = 0.5,
  Ω = Diagonal([0.04,0.04,0.36,0.36,0.04,0.04]),
  σ = 0.1
  )
Random.seed!(123)
sims = simobs(two_parallel_drugs, pop, param)

plot(sims)

```

 ![image](https://canada1.discourse-cdn.com/flex030/uploads/pumas/original/1X/96e65f104855d4791c9a9759eac4bb41bb5668bd.jpeg)

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<div class="post-metadata">

**Author:** ![sai\_matcha](https://yyz2.discourse-cdn.com/flex030/user_avatar/discourse.pumas.ai/sai_matcha/32/297_2.png) [@sai\_matcha](https://discourse.pumas.ai/u/sai_matcha)\
**Post date:** [November 28, 2020, 5:12pm UTC](https://discourse.pumas.ai/t/bioavailability-clarification/440/5 "2020-11-28T17:12:37Z")

</div>

Thank you , Itz cleared my doubt.