Pharmacokinetics is hard ! Differences between clonazepam pills and liquid/drops

[aced126]

A higher cmax doesnt mean higher BA. Possibly it could be from incomplete dissolution of the solid tablet form but seems unlikely. There should be no difference in distribution between the two, as once either reaches the bloodstream, they basically are the same. If you are looking at Vd (volume of distribution) you need to realize this is simply a PK parameter, and doesnt reflect any actual physiological volume. High Vd drugs simply mean a drug isnt confined simply to the blood but widely spread through various tissues. So a Vd of around 3-8 means the drug is confined to the blood (usually polar drugs or ones highly protein bound) and a large to very large Vd means it can be found in many tissues. So if the tablets had say a Vd of 80 and the liquid 90, it has very little actual relevance other than you can say both are highly distributed to various tissue.

How do different formulations result in different Vds? I am instinctively thinking that all would result in identical Vds.

 

[Kittycat5]

They should. I was just using that as an example to show a Vd that is high doesnt mean you can really infer anything more than drug A and drug B are both distributed to tissues and not confined to plasma/blood. I just used the two forms of Rivotril as an example, which I admit was confusing. The most basic equation is Vd = Dose/plasma concentration. So if we go on the idea clonazepam liquid really does have higher concentrations than the tabs, its Vd would actually be lower at equivalent doses. But Vd would more commonly be used to estimate plasma concentration not the other way around. You would know your dose, look up the Vd and calculate a concentration. Its a total PK parameter, useful in many equations, but in this case (the Rivotrl) it would tell you very little.

 

[Kdem]

While I'm not sure anyone can put this to use, here is at least one link that suggests that the preparation/formulation cause a change in drug distribution (CMME, CME, clonazepam oral solution, intravenous CME):

http://www.ncbi.nlm.nih.gov/pubmed/16419051

'Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain'

The introduction of that Rivotril solution is old, so very little data are available.