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Sunday, June 5, 2016

Diltiazem IV to PO Explained

One of the oldest posts on EMPharmD has finally received an update. One of the most prominent lessons I've learned since graduating residency years ago is that the more I learn, the more I realize I do not know, and seeking out help is not a sign of weakness, but a strength.  
Artist rendering of diltiazem formula investigation

As such, when I encountered a wall in trying to trace the origin of the diltiazem IV to PO estimations, I re-published the post on pharmacytimes.com, hoping someone smarter than me would help explain. That strategy paid off and Dr. Varela from Nova Southeastern University College of Pharmacy was gracious enough to give permission to publish his reply to me on this blog:

There is no one recommended conversion to an oral dosage regimen when using an intravenous drip of diltiazem. You elegantly stated one estimate of total daily oral dose from the standard diltiazem drip rates:

   5 mg/hr                            180 mg/day
   7.5 mg/hr                         255 mg/day  (the 260 mg is rounded, [7.5 mg/hr x 30] + 30 = 255 mg/day)
   10 mg/hr                          330 mg/day
   15 mg/hr                          480 mg/day

The formula: Oral dose = {IV drip rate (mg/hr) x 3 + 3} x 10 can be algebraically expanded to obtain
TDD = 30 (rate) + 30 

Note how it looks like the linear form y= mx + b.

Just use linear regression software, making “x” the IV rate and the corresponding “y” the total oral daily dose; the slope (m) will be 30 and the y-intercept (b) will also be 30.  Letting y = TDD (Total Daily Dose) in the oral regimen, slope = 30, x = drip rate in mg/hr, and the y-intercept = 30 the “linear” representation (of the small table) is obtained. There are no references for this formula since it just a linear regression transformation that anyone can perform using any scientific calculator. There is no mystery, nor clinical studies, just linear regression.

I do have to caution that diltiazem has nonlinear pharmacokinetics and linear regression would not be appropriate; however there is no harm in just "plotting" the above 4 sets of points and obtaining an easy "mnemonic formula". It is not clinical just math.

Excellent description on how to tapper the iv drip and "bridging' to the oral diltiazem regimen. 

To be complete using pharmacokinetic principles  and a bioavailability factor of 40% for immediate-release diltiazem another formula: MD/day = 60 R: R = infusion rate in mg/hr, MD = oral maintenance dose. This gives a much higher oral dosing regimen.

Thank you

Jorge Varela, PharmD
Department of Pharmaceutical Sciences
NSU College of Pharmacy

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