I don't know. But a possible (despite not usual) way to do it is tiratrate e.v. morphine with a TCI pump. And, also, it is possible to measure the plasma amount of drug. An article I published in 1999 (available here on RG), is about the Target Congrolled Infusion. We tested propofol and other drugs with known pharmacocinetic bi-tri compartimental models. The pump algorithm predicted the plasma concentration of drugs, as we also performed plasma drug measurements. Hope this helps even I'm not sure. 

Someone needs to study plasma levels of people who are currently taking oral morphine.

The law is for leisure drug abusers?

There should be exemptions for persons requiring therapeutic oral morphine.  Although disease processes, other medications and comorbidities should added into the equation regarding the persons cognitive ability/impairment.

Bioavailability of Oral Morphine is 35%. Plasma volume in 70 kg person is around 3.5 Lt and Plasma Half life is 2-4 hrs. If we know the volume of distribution then we can estimate the oral morphine dose 

You can work out the predicted dose based upon population values for Vd, clearance and therefore halt life of the morphine dose. Depends on why you want to do this. Ultimately, morphine clearance is highly dependant on renal function due to the fact that the major metabolites are really cleared. Thus it follows that whilst you can use kinetics to give an estimate the reality is this will vary in an actual patient because of patient specific pharmacokinetic factors that will influence how a dose in absorbed and cleared. Depends on why you need to know and how accurate you wish to be. 

A simple pharmacokinetics text book will guide you through the calculations required. 

There are IT solutions, which simulate specific kinetic situations like gastric stasis etc and those will also give you predicted profiles based on dosage programmes. 

thanks for responses thus far. I wonder how the DVLA will have reached its conclusion to set 80 micrograms as a blood plasma level threshold. I assume they will have based this on research.

We have a programme called SimCyp which would allow us to simulate a range of patients and therefore give a range of reasonable doses based upon renal function. Happy to discuss further if you wish. Basically, what I would suggest doing would be to use a range of reasonable values for clearance representing a range of 'normal' patients and therefore you will get a range of doses representing this plasma level. I suspect that is what would suit your needs

Hi,

As other collegues have said, it ´s possible to calculate the plasmatic concentration of a drug knowing the vD. The answers are all very intersting. Thanks!!!

But to reach an adecuate analgesia with oral morphine, there are others variables that may be important. The ratio between metabolites, especially M6G and M3G is important to analgesia, and is not predictable for the individual patient just calculating the plasmatic concentration.

Bioavailability is not constant for all the patients, and drug interactions may be important too.

Given that there´s no ceiling effect with morphine, it doesn´t seems very reasonable to set a limit for plasma concentration from the clinical point of view.

Best regards.

The influence of M6G (about 10% of an oral dose) and M3G (about 90% of an oral dose) is interesting and indeed is subject to variability specifically through phenotypic variation around the enzyme responsible for glucuronidation of the parent compound. The general view (as always there are counter views) is that M3G does not contribute to the analgesic effect or the sedative effect of morphine, but there is some evidence to suggest it could possibly act as a partial antagonist to some of the effects of morphine.   There is also some evidence to show that M6G could be more potent in analgesic terms and in terms of causing emesis than the parent compound, again this view can be countered. All of this said, I am not sure how specifically this affects this issue (the DVLA) and of course irrespective of all of this the analgesic effect of morphine is subject to the development of tolerance and thus is variable full stop, particularly if the subject is not opiate naive. As I said in my previous answer we are happy to calculate the likely range of doses, contact details can be found with a Google search