A look at the basics of biopharmaceutics.

1. George Wild Science of Medicines
1
Introduction to Biopharmaceutics
Biopharmaceutics concernsitself withhow the physicochemical propertiesof adrug,the dosage
formand the route of administrationall affectthe rate andextentof absorption.Exceptforwhena
drug isadministeredbythe IV route,a drug mustpass a barrierto enterthe systemiccirculation.
Once there,the drug will partitionbetweenredbloodcellsandplasma,andagaininthe plasma
betweenalbumenproteinandwater/fluid.The concentrationof unbounddrug(the druginthe
fluid) isinequilibriumwiththe concentrationof drugat the active/therapeuticsite of actioninthe
body;thisis the proportionof drugin the bloodthatwill passintotissue fluidandreachthe target
cell membranes.The concentrationof drugat the site of action iscommonlyestimatedusing the
concentrationof drugpresentinthe plasma,eventhoughthe total plasmaconcentrationisknown
to be differenttothe concentrationpresentatthe targetcells.Thisvalue isusedasa surrogate
simplybecause the methodsinvolvedinobtainingthe value forthe concentrationof unbounddrug
inthe plasmaare too complicatedtobotherwith.
The concentrationavailable foruse inthe plasmawill be determinedbythree things;the amountof
drug originallyadministeredthatwasabsorbedintothe bloodstream, the amountof drugthat has
beenabsorbedintotissuesotherthanthose forwhichitwas intendedandthirdly;the rate of
eliminationof the drugfromthe body. The studyof the absorption,distribution,metabolismand
elimination(ADME) of adrug iscalledpharmacokineticsandisthe foundationof manystudies
undertakenbeforeadrug islicensed.The studyof how these factorsinfluence physiological
behavioursinthe bodyiscalledpharmacodynamicsandit’softenthe case thatstudiescentred on
pharmacokineticaspectsof adrug will use pharmacodynamicsmarkersinordertoassessthe clinical
or therapeuticeffectivenessof adrug.
Bioavailability
Bioavailabilityisthe conceptof a certainamountof drugbeingpresentandbiologicallyavailable for
use inthe body,followinganadministereddose.There’sonlyone route of administrationinwhicha
drug issaidto be 100% bioavailable,andthat’sthe IV route because the entire syringe ordrugis
emptieddirectlyintothe systemiccirculation(whichisconsideredtoonlybe venousandarterial i.e.
not mesenteric).Allotherroutesof administrationpresentbarrierstoabsorptionwhichmustfirstbe
overcome before the drugcanenterthe systemiccirculation.Foradrug to be completelyabsorbed
across a biological membraneandenterthe systemiccirculationcompletelyunchangedisincredibly
rare as the mechanismsandbarriersthatmust be crossedare inplace to preventexactlywhatwe’re
tryingto do; puta foreignbodyinsideourtissues.This wouldbe especiallydifficultwhenadrugis
administeredorally,asthe drugwouldhave tobe completelyreleasedfromthe dosage form,
dissolve andbe completelystable inthe GIfluids, passunhinderedacrossthe membranesinthe GI
tract and thenpass throughthe mesentericcirculationandlivercompletelyunchanged.Thissimply
cannot happen.
Whencomparingthe bioavailabilityof drugs,it’susefultohave a benchmark/goldstandardtowhich
we can compare ourresult,because of the wide arrayof dosage formsandroutesof administration
that are available tous.This“absolute”bioavailabilitycomparesthe bioavailabilityof adrug
followingadministrationthroughanon-IV (i.e.oral,buccal,sublingual,ophthalmic,nasal,aural,
topical,transdermal, rectal,vaginal,intramuscular,subcutaneous,depot) route withthe

2. George Wild Science of Medicines
2
bioavailabilityof the same druginthe same concentrationwhenadministeredthroughthe
intravenousroute.
- It’simportantto knowthat the term“bioavailability”referstothe percentage of drug
circulatingunchangedthe bodywithregardtothe amount originallyadministered,whilst
the “bioavailabledose”isthe amountof drugin systemiccirculation.
The terms listedabove canonlybe appliedtodrugsthatare administeredalreadyintheir
therapeuticallyactive form, i.e.we cannottalkaboutthe bioavailabilityof prodrugs,becauseby
theirnature,theymustbe alteredinthe bodyfor themtobecome therapeuticallyactive andsothis
isa directcontradictionof the definitionof bioavailability;the percentage of the drugadministered
that reachesthe systemiccirculationunchanged.
In discoveryanddevelopment,itmaybe the case that a drug showstherapeuticactivityinsmall in
vitrostudies,butstudiesmustbe undertakentoassessthe extenttowhichfactorsof natural
variationwill affectthe final bioavailabilityof adrug. Thisisimportantbecause it’sall well andgood
for a drug to have a benefitata knownconcentration,butthisisuselessif,despite being
administered inthisconcentration,the requiredamountof drugneverreachessystemiccirculation.
There are a plethoraof factorsthat will affectthe bioavailabilityof adrug,for example;the dosage
formin whichthe drug isadministered,the physicochemical propertiesof the drug,the formulation
of the drug,the route bywhichit isadministered,the frequencyof administration,the co-
administrationof drugs,interactionswiththe drugandself-medicationissues,the age of the patient,
the counsellingthe patienthasreceivedonhow totake the drug,foodor drinkthat istakenwiththe
medicine,the severityof the condition,comorbidities,lifestyleandmore.
In reality,asimple plasmaconcentration-time curve canbe usedto gatherinformationona
therapeuticwindowwithinwhichthe maximumconcentrationinthe bloodplasma(Cmax) shouldlie.
It’simportantto recognise thatthe amountof drug administeredisnotnecessarilythe amountof
drug that ispresentinthe blood(isbioavailable).Thisnote has more weightwhenitcomes to
topicallyandorallyadministereddrugsthanintravenous, whichwe know tobe 100% bioavailable.
Above the maximumsafe concentrationwe begintosee side-effectsandtoxicity,below itandwe
are lookingatsub-therapeuticdosesandhomeopathicprinciples.