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Pet Forum / Miscellaneous / Animal Health / February 2008Random calculations...
So I'm procrastinating studying and running various numbers to see if I could work out the origin behind some of the testing schedules for phenobarb levels. From http://www.canine-epilepsy.com/Phenobarbital.html Ideally trough levels should be taken 14, 45, 90 & and 180 days after starting PB therapy and at least every 6 months thereafter. According to various sources I've found online, the half life of phenobarb in the body is between 53 and 118 hours (depending on the animal), and tends to increase with prolonged use. Lets start with the 14 day measure. At day 14, based on simple half life calculations, the low half life value should give a 98.9% of the expected long term concentrations. The longer half life value will give 87.1% of the expected steady state levels.(if the half life is on the high end, the expected concentration is roughly twice the value for teh short half life scenario). Similar levels are reached for the long half life case at about day 30. At day 45, with simple half life calculations, the long half life scenario reaches 99.94% of its expected long term concentation (interestingly, if we assume the dosing my dog is getting...60mg twice a day) this is the exact day where the number of circulating mgs reaches the correct 'integer' value. Presumably the later tests will show how the dog is reacting to being on phenobarb long term, and allow any adjustments to be made. Dale "Dale Atkin" <labrador1@ibycus.com> said in alt.med.veterinary: > According to various sources I've found online, the half > life of phenobarb in the body is between 53 and 118 hours > (depending on the animal) Generally accepted is 36 hours (maybe to be conservative) and is why it's dosed at 12 hour intervals (one-third the half- life) to even out the downs. > and tends to increase with > prolonged use. That's interesting and new to me. > Presumably the later tests will show how the dog is > reacting to being on phenobarb long term, and allow any > adjustments to be made. Let's start at the beginning: describe exactly her symptoms during her first observed seizure. How long, frequency, did she poo or pee, did she react to you? Postictal is important, too. How quickly Rocky recovered from his seizures told me a lot.  Signature--Matt. Rocky's a Dog. > "Dale Atkin" <labrador1@ibycus.com> said in > alt.med.veterinary: [quoted text clipped - 6 lines] > is why it's dosed at 12 hour intervals (one-third the half- > life) to even out the downs. Interesting, the page I was looking at was a human one, so its possibly different in dogs. The lower the half life, the lower the steady state amount, but also the sooner 'steady state' is reached. So with a 36 hour half life, 98% of the 'steady state' is reached at day 8. >> and tends to increase with >> prolonged use. > > That's interesting and new to me. Heres a reference http://www.sdrl.com/druglist/phenobarbital.html >> Presumably the later tests will show how the dog is >> reacting to being on phenobarb long term, and allow any [quoted text clipped - 5 lines] > too. How quickly Rocky recovered from his seizures told me a > lot. First noticed any symptoms about a year ago. In retrospect what I saw then was his first seizure, I didn't know it at the time, as I'd never seen a seizure of any kind before, and blamed it on the cold weather. What I saw was the following: We were walking along down by Bearspaw dam, out past the end of the spill way, when he stopped, and he seemed to all of a sudden go lame on his front left leg. Attempts to get him to walk were met with stumbling. He was most certainly aware of me, and seemed to calm down a bit as I spoke to him. I picked him up and decided I was going to have to carry him back to the car. Got a few feet, when I realized I was going to have to put him down to walk down a fairly steep set of rocks. I put him down, and he was fine and ran off happily like nothing had happend. The whole episode, start to finish lasted about a 2-3 minutes. (no pee, no poo) I next noticed something about 6 months later. We were houseboating, he ran off the boat, and up the beach Similar kind of symptoms. I hugged him for a while, and then he was all better. Over the coming months, his seizures got more frequent, and culminated (I thought) with the vet finding some really nasty arthritis in his front left elbow. Since the end of December, his symptoms have mostly been going away. He's much better behaved at the park than he had been, less grouchy etc, but while the incidence of his seizures (recall I still didn't know they were seizures... they'd been more or less assigned to shooting pain down his leg related to the arthritis) had decreased, they still happend (about once a week on average now... prior to the treatment for his elbow it was just about every other day). I was a little concerned that they didn't seem to be correlated with when I'd expect him to be in pain. They seemed more than anything to be correlated with excitement than with exertion. Well yesterday it happend while I was at the clinic. I'd brought him in with me because he'd been having diarhea, and I didn't want to leave him alone in the car for 4 hours unattended, and besides it was -30C. He'd barked a couple of times in his kennel, and I obligingly took him out to poop. After the second time, he was quite excited, and thats when he had his seizure. I called the vet out of an appointment to have a look, and he confirmed what I'd been worried about, that they were seizures. I think that more or less brings you up to speed. (Oh, the barking I don't think is correlated with the onset of the seizure, I think it was more "I'm bored" than anything else). Dale Dale This looks like an interesting article. I'll have to pull up the complete version sometime, but the abstract is certainly interesting. http://avmajournals.avma.org/doi/abs/10.2460/javma.2000.217.200 Dale > So I'm procrastinating studying and running various numbers to see if I > could work out the origin behind some of the testing schedules for [quoted text clipped - 27 lines] > > Dale "Dale Atkin" <labrador1@ibycus.com> said in alt.med.veterinary: > This looks like an interesting article. I'll have to pull > up the complete version sometime, but the abstract is > certainly interesting. > > http://avmajournals.avma.org/doi/abs/10.2460/javma.2000.217. > 200 It is interesting. Are we still talking about PB half-life? I noticed that the article spoke to testing the PB level over a relatively short period - the trough level tests didn't go beyond the 6 hour mark. Being a layman, I'm assuming that trough refers to the lowest level. I'm a big believer in going for whatever my trusted vet suggests, and then--from there--bouncing ideas. Signature--Matt. Rocky's a Dog. > "Dale Atkin" <labrador1@ibycus.com> said in > alt.med.veterinary: [quoted text clipped - 12 lines] > beyond the 6 hour mark. Being a layman, I'm assuming that > trough refers to the lowest level. Yep. Thats exactly what through was refering to. Of particular interest is "There is no therapeutically relevant change in serum phenobarbital concentrations throughout a daily dosing interval in most epileptic dogs. Therefore, timing is not important when collecting blood samples to measure serum phenobarbital concentrations in most epileptic dogs treated long-term with phenobarbital. (J Am Vet Med Assoc 2000;217:200-204)" Basically what it is saying is that the time that you test the PB levels doesn't really matter with respect to when you last gave the pill. 91% of dogs fell within the same theraputic range independent of when the levels were checked. > I'm a big believer in going for whatever my trusted vet > suggests, and then--from there--bouncing ideas. I'm pretty much the same way, but I like to inform myself as much as possible. (one thing I can say for Erwin, is he sure is educational :)). Particularly what I'm trying to get a handle on (right now) is exactly how sensitive the PB levels are to dose timing. For example, if I'm an hour late, or an hour early, what impact will this have? Can I reconcile what I've read and been told to known facts regarding the kinetics of the drug. (I'm not planning on being late or early, but its always important to know what the consequences are of a mistake) Dale I wrote: >> the trough level tests didn't go >> beyond the 6 hour mark. This was my main concern. Signature--Matt. Rocky's a Dog. "Dale Atkin" <labrador1@ibycus.com> said in alt.med.veterinary: > Particularly what I'm trying to get a handle on (right now) > is exactly how sensitive the PB levels are to dose timing. > For example, if I'm an hour late, or an hour early, what > impact will this have? Some dogs are more reactive than others to off scheduled PB doses. The two most common alternatives are dividing the daily dose into three or adding Pottasium Bromide to the mix - the latter, especially, when cluster seizures are involved. Signature--Matt. Rocky's a Dog. Another interesting article... http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references& therow=156648 > So I'm procrastinating studying and running various numbers to see if I > could work out the origin behind some of the testing schedules for [quoted text clipped - 27 lines] > > Dale "Dale Atkin" <labrador1@ibycus.com> said in alt.med.veterinary: > Another interesting article... > http://grande.nal.usda.gov/ibids/index.php?mode2=detail&orig > in=ibids_references&therow=156648 How so? Signature--Matt. Rocky's a Dog. One thing I'm trying to get a handle on here is the kinetic of phenobarb in the system, and the various influences on absorbtion, and clearing. Some of the stuff I'm running in to, is for the moment beyond me, but I think I'm getting there. This particular article refers to how a dog's diet can influence the half life (and other kinetic parameters) of phenobarb in the system. In particular, the half life, and thus 'steady state' levels of phenobarb in the system were reduced when the dog was fed a protein restricted or a fat and protein restricted diet. It also give some much lower values for mean half life (t 1/2) than I've seen elsewhere (around 30 hours). Dale > "Dale Atkin" <labrador1@ibycus.com> said in > alt.med.veterinary: [quoted text clipped - 4 lines] > > How so? "Dale Atkin" <labrador1@ibycus.com> said in alt.med.veterinary: > This particular article refers to how a dog's diet can > influence the half life (and other kinetic parameters) of > phenobarb in the system. In particular, the half life, and > thus 'steady state' levels of phenobarb in the system were > reduced when the dog was fed a protein restricted or a fat > and protein restricted diet. More important than such levels, I think that such a dog needs a consistent diet (more difficult than one first thinks). Try throwing Potassium Bromide into the drug and diet equation and you'll understand why I'm so anal as to my epileptic dog's food. Signature--Matt. Rocky's a Dog. |
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