Aa
Houston, this is 13...
I am beginning to think about my end of treatment plan and looking for thoughts on the subject. HR has discussed the tapering topic in the past.....
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
by HR
"It needs to be understood that when stopping IFN, a new form of antiviral defense against possible HCV remnants needs to take hold and establish itself - the adaptive Tcell response, that up to this point was greatly aided by the direct effect of IFN on the hepatocytes and the local intrahepatic immune cells. With this IFN aid gone all the burden is on the Tcell response, that will typically get stronger if more remnant viruses are seen ( if they can be seen now, because new epitopes are now present) - with incredible sensitivity, but it takes time to come to full swing and it can furthermore, at this very critical moment, be paralyzed by the prominent absence of innate signals needed to get adaptive Tcell responses going after IFN is abruptly missing from the equation. Here is one more specific EXAMPLE how the Tcell effect depends on the presence of some Interferon: The presentation of the viral epitopes is performed - as described in detail in an earlier post- by the cellular proteasome and the class I MHC molecules that bind the peptide and bring it to the surface for recognition by the "cognate" Tcell receptors of the "cognate" Tcell patrolling the liver."
He also recommended adding Lactoferrin at this time to help the immune system come "back online". Has anyone tried this? And any opinions on other immune enhancing supplements? Thanks.
---------------------------
"Houston, we need to go over those re-entry procedures so there are no foul ups, so here is what you are going to do, give us whatever you got so we can look em over. We are all a bit tired up here... and the earths getting awfully big in the window...."
"13... this is Houston, we are going to get those procedures to you just as soon as we possibly can. Ken Mattingly is in the simulator as we speak..."
"Roger that Houston... Kens working on it..."
Worked for me, read all the pro’s and con’s back then on the topic of tapering from the various folks here with a big imprint from HR as to my reduction schedule and then went for it after completing the 48 weeks, took 4 weeks to complete but I got my SVR. Could I have reached the same outcome at the end of 48 with the abrupt stoppage, don’t know but then again I don’t have to answer that question. As part of the pre surgery physical my AST is 21 and ALT is 17 at 8 months post.
jasper
jasper
One other thing.
The point i was trying to make is that just because a Dr doesnt do something doesnt mean that a concept or theory doesnt have merit.
CS
The point i was trying to make is that just because a Dr doesnt do something doesnt mean that a concept or theory doesnt have merit.
CS
Either way it doesnt matter he nor anyone else does it.
And no i am not insuating anything. You over read it.
I actually like the way Shiffman treats.
CS
And no i am not insuating anything. You over read it.
I actually like the way Shiffman treats.
CS
Are you insinuating that Schiffman is incompetent.
Do you know hes really not in favor for the serumbased aproach, couldn´t it just be that the labs dont perform such tests as a standard just yet.
ca
Do you know hes really not in favor for the serumbased aproach, couldn´t it just be that the labs dont perform such tests as a standard just yet.
ca
The extracts below are interesting in regard to tapering
Review article: Pegylated interferons: chemical and clinical differences
Aliment Pharmacol Ther 2004; 20: 825–830.
PHARMACOKINETICS OF THE DIFFERENT PEG-IFNS
The differences in the basic chemistry of the PEG-IFNs are associated with significant differences in the pharmacokinetics and pharmacodynamics of the two drugs.
The 12 kDa PEG-IFNa-2b has a relatively rapid absorption (absorption half-life of 4.6 h, compared with 2.3 h for conventional IFNa-2b), a wide volume of distribution (approximately 0.99 L/kg) a peak-to-trough ratio of >10 (after multiple doses) and reduced clearance (725 mL/h compared with 6000 mL/h for the unmodified IFN).7
The 40 kDa PEG-IFNa-2a is absorbed more slowly (the absorption half-life is 50 h), has a restricted volume of distribution (8 L), a narrow peak-to-trough ratio of 1.5 (after multiple doses) indicating minimal fluctuation in serum concentration, and a markedly reduced rate of clearance (60 mL/h) when compared with non-PEG-IFN.8 Thus, PEG-IFNa-2b is quickly absorbed, circulates widely and declines to undetectable serum levels within a few days, whereas the 40 kDa
PEG-IFNa-2a is absorbed slowly, is restricted largely to the vasculature and well-perfused organs, such as the liver, and is still detectable in serum after a week. Table 2 lists the pharmacokinetic and pharmacodynamic differences between the two PEG-IFNs.
PegIntronPI
Pharmacokinetics: Following a single subcutaneous (SC) dose of PegIntron, the mean absorption half-life (t 1/2 ka) was 4.6 hours. Maximal serum concentrations (Cmax) occur between 15-44 hours post-dose, and are sustained for up to 48-72 hours. The Cmax and AUC measurements of PegIntron increase in a dose-related manner. After multiple dosing, there is an increase in bioavailability of PegIntron. Week 48 mean trough concentrations (320 pg/mL; range 0, 2960) are approximately 3-fold higher than Week 4 mean trough concentrations (94 pg/mL; range 0, 416). The mean PegIntron elimination half-life is approximately 40 hours (range 22 to 60 hours) in patients with HCV infection. The apparent clearance of PegIntron is estimated to be approximately
22.0 mL/hr•kg. Renal elimination accounts for 30% of the clearance.
Pegylation of interferon alfa-2b produces a product (PegIntron) whose clearance is lower than that of non-pegylated interferon alfa-2b. When compared to INTRON A, PegIntron (1 mcg/kg) has approximately a seven-fold lower mean apparent clearance and a five-fold greater mean half-life permitting a reduced dosing frequency. At effective therapeutic doses, PegIntron has approximately ten-fold greater Cmax and 50-fold greater AUC than interferon alfa-2b.
Below comes from two Pegasys Product Info Sheets
Pegasys-RBV PI
Elimination: After intravenous administration, the terminal half-life of PEGASYS in healthy subjects is approximately 60 hours compared to 3 to 4 hours for standard interferon. A mean elimination half-life of 160 hours (84-353 hours) at primary elimination phase was observed in patients after subcutaneous administration of PEGASYS. The elimination half-life determined after subcutaneous administration may not only reflect the elimination phase of the compound, but may also reflect the sustained absorption of PEGASYS.
Pegasys PI
Week 48 mean trough concentrations (16 ng/mL; range 4 to 28) at 168 hours post-dose are approximately 2-fold higher than week 1 mean trough concentrations (9 ng/mL; range 0 to 15). Steady-state serum levels are reached within 5 to 8 weeks of once weekly dosing. The peak to trough ratio at week 48 is approximately 2. The mean systemic clearance in healthy subjects given PEGASYS was 94 mL/h, which is approximately 100-fold lower than that for interferon alfa-2a (ROFERON-A). The mean terminal half life after sc dosing in patients with chronic hepatitis C was 80 hours (range 50 to 140 hours) compared to 5 hours (range 3.7 to 8.5 hours) for ROFERON-A.
The 60 hours Half-Life is via IV administration
Its 80 Hours Half-Life with SQ administration
The mean terminal half life after sc dosing in patients with chronic hepatitis C was 80 hours (range 50 to 140 hours)
Notice the elimination range “A mean elimination half-life of 160 hours (84-353 hours)”
The mean PegIntron elimination half-life is approximately 40 hours (range 22 to 60 hours) in patients with HCV infection.
So with PegIntron you basiclly would not have any form of natural taper as you would basically have none left by the time you finish off the Riba.
With Pegasys you do get a natural form of Taper but not for everyone.
So tapering off at the end of Tx still appears to be a valid theory to me.
Jim- I assume Shiffman would be advocating tapering which to my knowledge he doesn't.
Maybe this is for the same reason that he does not advocate dosing Riba according to serum concentration. Instead prefers dosing by weight still.
All the Best
CS
Review article: Pegylated interferons: chemical and clinical differences
Aliment Pharmacol Ther 2004; 20: 825–830.
PHARMACOKINETICS OF THE DIFFERENT PEG-IFNS
The differences in the basic chemistry of the PEG-IFNs are associated with significant differences in the pharmacokinetics and pharmacodynamics of the two drugs.
The 12 kDa PEG-IFNa-2b has a relatively rapid absorption (absorption half-life of 4.6 h, compared with 2.3 h for conventional IFNa-2b), a wide volume of distribution (approximately 0.99 L/kg) a peak-to-trough ratio of >10 (after multiple doses) and reduced clearance (725 mL/h compared with 6000 mL/h for the unmodified IFN).7
The 40 kDa PEG-IFNa-2a is absorbed more slowly (the absorption half-life is 50 h), has a restricted volume of distribution (8 L), a narrow peak-to-trough ratio of 1.5 (after multiple doses) indicating minimal fluctuation in serum concentration, and a markedly reduced rate of clearance (60 mL/h) when compared with non-PEG-IFN.8 Thus, PEG-IFNa-2b is quickly absorbed, circulates widely and declines to undetectable serum levels within a few days, whereas the 40 kDa
PEG-IFNa-2a is absorbed slowly, is restricted largely to the vasculature and well-perfused organs, such as the liver, and is still detectable in serum after a week. Table 2 lists the pharmacokinetic and pharmacodynamic differences between the two PEG-IFNs.
PegIntronPI
Pharmacokinetics: Following a single subcutaneous (SC) dose of PegIntron, the mean absorption half-life (t 1/2 ka) was 4.6 hours. Maximal serum concentrations (Cmax) occur between 15-44 hours post-dose, and are sustained for up to 48-72 hours. The Cmax and AUC measurements of PegIntron increase in a dose-related manner. After multiple dosing, there is an increase in bioavailability of PegIntron. Week 48 mean trough concentrations (320 pg/mL; range 0, 2960) are approximately 3-fold higher than Week 4 mean trough concentrations (94 pg/mL; range 0, 416). The mean PegIntron elimination half-life is approximately 40 hours (range 22 to 60 hours) in patients with HCV infection. The apparent clearance of PegIntron is estimated to be approximately
22.0 mL/hr•kg. Renal elimination accounts for 30% of the clearance.
Pegylation of interferon alfa-2b produces a product (PegIntron) whose clearance is lower than that of non-pegylated interferon alfa-2b. When compared to INTRON A, PegIntron (1 mcg/kg) has approximately a seven-fold lower mean apparent clearance and a five-fold greater mean half-life permitting a reduced dosing frequency. At effective therapeutic doses, PegIntron has approximately ten-fold greater Cmax and 50-fold greater AUC than interferon alfa-2b.
Below comes from two Pegasys Product Info Sheets
Pegasys-RBV PI
Elimination: After intravenous administration, the terminal half-life of PEGASYS in healthy subjects is approximately 60 hours compared to 3 to 4 hours for standard interferon. A mean elimination half-life of 160 hours (84-353 hours) at primary elimination phase was observed in patients after subcutaneous administration of PEGASYS. The elimination half-life determined after subcutaneous administration may not only reflect the elimination phase of the compound, but may also reflect the sustained absorption of PEGASYS.
Pegasys PI
Week 48 mean trough concentrations (16 ng/mL; range 4 to 28) at 168 hours post-dose are approximately 2-fold higher than week 1 mean trough concentrations (9 ng/mL; range 0 to 15). Steady-state serum levels are reached within 5 to 8 weeks of once weekly dosing. The peak to trough ratio at week 48 is approximately 2. The mean systemic clearance in healthy subjects given PEGASYS was 94 mL/h, which is approximately 100-fold lower than that for interferon alfa-2a (ROFERON-A). The mean terminal half life after sc dosing in patients with chronic hepatitis C was 80 hours (range 50 to 140 hours) compared to 5 hours (range 3.7 to 8.5 hours) for ROFERON-A.
The 60 hours Half-Life is via IV administration
Its 80 Hours Half-Life with SQ administration
The mean terminal half life after sc dosing in patients with chronic hepatitis C was 80 hours (range 50 to 140 hours)
Notice the elimination range “A mean elimination half-life of 160 hours (84-353 hours)”
The mean PegIntron elimination half-life is approximately 40 hours (range 22 to 60 hours) in patients with HCV infection.
So with PegIntron you basiclly would not have any form of natural taper as you would basically have none left by the time you finish off the Riba.
With Pegasys you do get a natural form of Taper but not for everyone.
So tapering off at the end of Tx still appears to be a valid theory to me.
Jim- I assume Shiffman would be advocating tapering which to my knowledge he doesn't.
Maybe this is for the same reason that he does not advocate dosing Riba according to serum concentration. Instead prefers dosing by weight still.
All the Best
CS
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