Aa
Measurement of VL in first 12 wks of treatment
I would like to know how important it is to all of you to know your exact VL during treatment at 4 and 8 weeks. If you have a PCR that measures down to <50IU/ml, are you content with a Pass/Fail until that week 12?
This is the scenario I'm in for and I'm not happy about it, I want to know my exact VL count at 4 weeks and 8 weeks if I fail, as in I'm above <50IU/ml. Is this reasonable or am I getting uptight for nothing? I'm thinking if I know at 4 weeks that I'm not doing so well, I can ask the doctor to alter my treatment to increase my odds. Then I can measure again at 8 weeks how it's going. A pass/fail doesn't give me enough information, I'm thinking. Am I off-base there? Hard to know if I'm letting emotions get in the way of clear thinking at the moment.
(I posted all my questions in one post on the other side..but way too much to slog through I'm thinking so I'm breaking it out individual posts for the questions that are on my mind.)
This is the scenario I'm in for and I'm not happy about it, I want to know my exact VL count at 4 weeks and 8 weeks if I fail, as in I'm above <50IU/ml. Is this reasonable or am I getting uptight for nothing? I'm thinking if I know at 4 weeks that I'm not doing so well, I can ask the doctor to alter my treatment to increase my odds. Then I can measure again at 8 weeks how it's going. A pass/fail doesn't give me enough information, I'm thinking. Am I off-base there? Hard to know if I'm letting emotions get in the way of clear thinking at the moment.
(I posted all my questions in one post on the other side..but way too much to slog through I'm thinking so I'm breaking it out individual posts for the questions that are on my mind.)
79x2=158+.5=158.5+1.5+160+4=164+.5=164.5+3.73=168.23 divided 2=84.115-.5=84.615-3.73=80.885-.5=80.385 subtract 1.385 error rate of absorption between 3 and 4 hours =79 hours of half life for a single dose from intake until total elimination of the body. I think?
jasper
jasper
I don't quite understand what "single-dose half-lives of absorption, distribution" means. My pharmacist said that absorption starts at 0.05 hours after oral intake and that the ribavirin is distributed throughout the body by 3 - 4 hours. What does half-life mean in this context?
The figures in Mr Liver's article above "The Clinical Pharmacology of Ribavirin" seem to be the same as those my pharmacist gave to me as information directly from Schering-Plough.
"Ribavirin is rapidly absorbed following oral administration (mean time to maximum concentration [Tmax] = 1.5 hours), followed by rapid distribution and prolonged elimination phases (single-dose half-lives of absorption, distribution, and elimination are 0.05, 3.73, and 79 hours, respectively)."
I find the differentiation in the article between duration of half-life for single dose and multiple dosing interesting: 79 hours vs 298 hours. 298 hours equals 12 days and 10 hours. (Kcmike mentioned a half life of 21 days in another thread. Was that incorrect?) 298 hours would explain why many seem to be feeling better 2 weeks post tx.
Notice also the mention of approximately 4 weeks to reach steady-state ribavirin concentration. In other contexts here on Medhelp 5 months have been mentioned. Which is correct?
And lastly notice the mention of approximately 15 half-lives (6 months) to ensure no effect on fetus.
"During multiple dosing, ribavirin accumulates extensively in plasma, with a ratio of multiple-dose to single-dose AUC at 12 hours (AUC12hr) of 6.[17] Following dosing with 600 mg twice daily, steady-state ribavirin concentration was reached by approximately 4 weeks, with mean steady-state plasma concentrations of 2,200 ng/mL. After discontinuation of dosing there was a washout half-life of 298 hours.[17] The extended washout period likely reflects slow elimination from nonplasma compartments (Figure 5). The fact that the multiple-dose ribavirin half-life (298 hours) is considerably longer than the single-dose half-life (79 hours) means that it is not possible to predict (ie, model) multiple-dose ribavirin pharmacokinetic parameters based on single-dose parameters."
"The extensive accumulation of ribavirin nucleotides and their slow dephosphorylation contribute to the long half-life following multiple dosing (approximately 300 hours). To prevent potential teratogenic effects, we have estimated that 6 months (approximately 15 half-lives) is required to ensure a complete washout following cessation of dosing."
"Ribavirin is rapidly absorbed following oral administration (mean time to maximum concentration [Tmax] = 1.5 hours), followed by rapid distribution and prolonged elimination phases (single-dose half-lives of absorption, distribution, and elimination are 0.05, 3.73, and 79 hours, respectively)."
I find the differentiation in the article between duration of half-life for single dose and multiple dosing interesting: 79 hours vs 298 hours. 298 hours equals 12 days and 10 hours. (Kcmike mentioned a half life of 21 days in another thread. Was that incorrect?) 298 hours would explain why many seem to be feeling better 2 weeks post tx.
Notice also the mention of approximately 4 weeks to reach steady-state ribavirin concentration. In other contexts here on Medhelp 5 months have been mentioned. Which is correct?
And lastly notice the mention of approximately 15 half-lives (6 months) to ensure no effect on fetus.
"During multiple dosing, ribavirin accumulates extensively in plasma, with a ratio of multiple-dose to single-dose AUC at 12 hours (AUC12hr) of 6.[17] Following dosing with 600 mg twice daily, steady-state ribavirin concentration was reached by approximately 4 weeks, with mean steady-state plasma concentrations of 2,200 ng/mL. After discontinuation of dosing there was a washout half-life of 298 hours.[17] The extended washout period likely reflects slow elimination from nonplasma compartments (Figure 5). The fact that the multiple-dose ribavirin half-life (298 hours) is considerably longer than the single-dose half-life (79 hours) means that it is not possible to predict (ie, model) multiple-dose ribavirin pharmacokinetic parameters based on single-dose parameters."
"The extensive accumulation of ribavirin nucleotides and their slow dephosphorylation contribute to the long half-life following multiple dosing (approximately 300 hours). To prevent potential teratogenic effects, we have estimated that 6 months (approximately 15 half-lives) is required to ensure a complete washout following cessation of dosing."
..........I keep trying to tell them that it's not covered and I want to PAY for it. They don't know how to deal with out of the box ...............
Glad you got the 'script', now hope you get it done!
I had a woman Dr. for years, loved her! She left and went to another office, they don't take my (crummy) insurance. I tried to see her and to pay CASH! They don't take CASH??? (self pay!) I said "okay, so if I had 20 million bucks and want to pay CASH for everything, I can't?" .....'No mam, we don't take cash, self pay'! I haven't been able to get past them just to talk to her! Sending her a letter as she will be amazed what has come of all the 'other' office's mistakes, and want her opinion on some things! She was the kind of Dr. that when she ordered a test for you and you didn't go, she'd call you herself and say "WHY haven't you done this? Get over there and do this!"
Pretty bad when cash doesn't work!
LL
Glad you got the 'script', now hope you get it done!
I had a woman Dr. for years, loved her! She left and went to another office, they don't take my (crummy) insurance. I tried to see her and to pay CASH! They don't take CASH??? (self pay!) I said "okay, so if I had 20 million bucks and want to pay CASH for everything, I can't?" .....'No mam, we don't take cash, self pay'! I haven't been able to get past them just to talk to her! Sending her a letter as she will be amazed what has come of all the 'other' office's mistakes, and want her opinion on some things! She was the kind of Dr. that when she ordered a test for you and you didn't go, she'd call you herself and say "WHY haven't you done this? Get over there and do this!"
Pretty bad when cash doesn't work!
LL
I don’t know if this has been posted before but may shed some light on the European medical community’s thoughts on the 4, 8, 12 pcr testing and shorter tx duration for the geno 1’s
jasper
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Individualized Treatment Duration for HCV Meets With Success
NEW YORK (Reuters Health) Jan 15 - In patients with hepatitis C virus (HCV), individualizing the duration of peginterferon/ribavirin treatment yields success rates similar to standard 48-week treatment, thus sparing unnecessary costs and side effects, according to results of two randomized controlled studies published in the January issue of Hepatology.
In one study, Dr. Alessandra Mangia from "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy, and colleagues treated 696 patients with HCV genotype 1 with peginterferon alfa-2a (180 g/week) or peginterferon alfa-2b (1.5 g/kg/week), plus ribavirin (1,000 to 1,200 mg/day). Patients were randomized to treatment for 48 weeks (the standard treatment group; n = 237) or for 24, 48 or 72 weeks if HCV-RNA was undetectable at 4, 8, or 12 weeks, respectively (the variable treatment group; n = 459).
According to the investigators, results showed "equivalent rates of lasting viral clearance after therapy administered for the standard 48-week length or a variable duration tailored on the first undetectable HCV RNA during the initial 12 weeks of therapy."
Nearly 49% of patients receiving variable treatment based on detectable HCV RNA achieved a sustained virologic response, compared with 45% of patients in the standard treatment group (p = 0.37), Dr. Mangia and colleagues report.
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Meanwhile, in a study of 428 patients with HCV genotype 2 or 3, researchers from Norway randomly assigned patients who achieved a virologic response after 4 weeks peginterferon alfa-2b (1.5 g/kg) weekly and ribavirin (800 to 1,400 mg/day) to complete either 14 weeks or 24 weeks of treatment.
In intention-to-treat analysis, Dr. Olav Dalgard from Ulleval University Hospital, Oslo and colleagues found that 81.1% of patients in the 14-week treatment arm and 90.7% in the 24-week arm achieved a sustained viral response.
Among patients with an HCV RNA test 24 weeks after the end of treatment, 86.3% of the 14-week treatment group and 93.2% of the 24-week treatment group had a sustained viral response.
"In conclusion, we cannot formally claim that 14 weeks treatment is non-inferior to 24 weeks treatment," Dr. Dalgard and colleagues write. "However, the sustained virologic response rate after 14 weeks treatment is high, and although longer treatment may give a slightly better sustained viral response rate, we believe considerable economical savings, good response to re-treatment, and less side effects make it rational to treat patients with genotype 2 or 3 and rapid viral response for only 14 weeks."
Hepatology 2008.
jasper
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Individualized Treatment Duration for HCV Meets With Success
NEW YORK (Reuters Health) Jan 15 - In patients with hepatitis C virus (HCV), individualizing the duration of peginterferon/ribavirin treatment yields success rates similar to standard 48-week treatment, thus sparing unnecessary costs and side effects, according to results of two randomized controlled studies published in the January issue of Hepatology.
In one study, Dr. Alessandra Mangia from "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy, and colleagues treated 696 patients with HCV genotype 1 with peginterferon alfa-2a (180 g/week) or peginterferon alfa-2b (1.5 g/kg/week), plus ribavirin (1,000 to 1,200 mg/day). Patients were randomized to treatment for 48 weeks (the standard treatment group; n = 237) or for 24, 48 or 72 weeks if HCV-RNA was undetectable at 4, 8, or 12 weeks, respectively (the variable treatment group; n = 459).
According to the investigators, results showed "equivalent rates of lasting viral clearance after therapy administered for the standard 48-week length or a variable duration tailored on the first undetectable HCV RNA during the initial 12 weeks of therapy."
Nearly 49% of patients receiving variable treatment based on detectable HCV RNA achieved a sustained virologic response, compared with 45% of patients in the standard treatment group (p = 0.37), Dr. Mangia and colleagues report.
"This study shows that in HCV genotype 1, treatment duration should be tailored to the 12-week on-treatment virologic response," Dr. Mangia and colleagues write. "HCV RNA should be monitored qualitatively at week 4 to identify patients with the highest likelihood of response, and at weeks 8 and 12 to determine if extended duration may be required," they conclude.
Meanwhile, in a study of 428 patients with HCV genotype 2 or 3, researchers from Norway randomly assigned patients who achieved a virologic response after 4 weeks peginterferon alfa-2b (1.5 g/kg) weekly and ribavirin (800 to 1,400 mg/day) to complete either 14 weeks or 24 weeks of treatment.
In intention-to-treat analysis, Dr. Olav Dalgard from Ulleval University Hospital, Oslo and colleagues found that 81.1% of patients in the 14-week treatment arm and 90.7% in the 24-week arm achieved a sustained viral response.
Among patients with an HCV RNA test 24 weeks after the end of treatment, 86.3% of the 14-week treatment group and 93.2% of the 24-week treatment group had a sustained viral response.
"In conclusion, we cannot formally claim that 14 weeks treatment is non-inferior to 24 weeks treatment," Dr. Dalgard and colleagues write. "However, the sustained virologic response rate after 14 weeks treatment is high, and although longer treatment may give a slightly better sustained viral response rate, we believe considerable economical savings, good response to re-treatment, and less side effects make it rational to treat patients with genotype 2 or 3 and rapid viral response for only 14 weeks."
Hepatology 2008.
Thanks for the heads up on this other article, I will also add that to the mix of my reading.
As for my tests. I wish it were that simple. I'm dealing with labs who don't do private testing for people. You'd think I could find one. I'm working on it. I'll be widening my search to the U.S. soon, simply so that I know what options are available.
The labs here are used to doing testing under government guidelines and protocols. What I'm asking for falls outside of that. So I walk in and say I want this done and I want to pay for it and they say "oh no...you don't have to pay for that, the government does." Then I launch into my spiel and I say that what I want is different than what the government pays for and how can I get this test done and pay for it myself? So far I've been met with blank stares and frustration on their part at such a seemingly simple question. They have a standard form to fill out for HCV PCR's and they have no procedure outside of that. The last place I went, she said " I don't KNOW how to give you what you want!" and I told her that's fine...but someone up above her must. And she gave me a couple of phone numbers to call. And I'm chipping my way through a system that operates on standard protocols when what I want is non-standard. The next phone call is to the lab that actually does the testing on the blood itself. And that happens to be the Public Health lab....as apparently I'm told not just any lab can do HCV RNA testing. And that's where it's done here. Argh. By the time I'm done...I'll have yet another educational experience under my belt.. but it's worth it because, well, of what I hope to accomplish in the bigger picture as a result and I'll leave it at that.
I'll keep in mind what you've said and pull it out as a stratagem if it fits within what they're willing to do. I just need to know how to pay for what I want and then get a process in place to be able to have me and others follow it.
As for my tests. I wish it were that simple. I'm dealing with labs who don't do private testing for people. You'd think I could find one. I'm working on it. I'll be widening my search to the U.S. soon, simply so that I know what options are available.
The labs here are used to doing testing under government guidelines and protocols. What I'm asking for falls outside of that. So I walk in and say I want this done and I want to pay for it and they say "oh no...you don't have to pay for that, the government does." Then I launch into my spiel and I say that what I want is different than what the government pays for and how can I get this test done and pay for it myself? So far I've been met with blank stares and frustration on their part at such a seemingly simple question. They have a standard form to fill out for HCV PCR's and they have no procedure outside of that. The last place I went, she said " I don't KNOW how to give you what you want!" and I told her that's fine...but someone up above her must. And she gave me a couple of phone numbers to call. And I'm chipping my way through a system that operates on standard protocols when what I want is non-standard. The next phone call is to the lab that actually does the testing on the blood itself. And that happens to be the Public Health lab....as apparently I'm told not just any lab can do HCV RNA testing. And that's where it's done here. Argh. By the time I'm done...I'll have yet another educational experience under my belt.. but it's worth it because, well, of what I hope to accomplish in the bigger picture as a result and I'll leave it at that.
I'll keep in mind what you've said and pull it out as a stratagem if it fits within what they're willing to do. I just need to know how to pay for what I want and then get a process in place to be able to have me and others follow it.
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