Split dosing... Maybe I need to titerate up...

[Aliakaraza]

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

 

[CranberryRocker]

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

 

[woundcarping]

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

If side effects are holding you back, that's one thing—but when they aren't, go ahead and titrate up.

How long have you been at 7.5mg?

What do your stats say—starting, current, and goal?

CranberryRocker said:

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

Whether you take it once weekly or split it, the area under the curve and the average level come out the same.

The usual thinking is that peaks are what cause sides, while troughs need to stay high enough to keep efficacy.

 

[Skidude]

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

 

[Aliakaraza]

woundcarping said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

If side effects are holding you back, that's one thing—but when they aren't, go ahead and titrate up.

How long have you been at 7.5mg?

What do your stats say—starting, current, and goal?

CranberryRocker said:

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

Whether you take it once weekly or split it, the area under the curve and the average level come out the same.

The usual thinking is that peaks are what cause sides, while troughs need to stay high enough to keep efficacy.

Mid-February was my start point at 262lbs; I'm at 227lbs now, and lately the scale has been stubborn... the same LB keeps coming and going.

I began 7.5mg on 2nd of May — hadn't realized I'd been on it for so long... Suppression definitely doesn't feel anywhere close to what it was before... Perhaps I'll raise the doseage and see how things go, and I'll map it on GLP1 and see...

 

[Skidude]

Aliakaraza said:

woundcarping said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

If side effects are holding you back, that's one thing—but when they aren't, go ahead and titrate up.

How long have you been at 7.5mg?

What do your stats say—starting, current, and goal?

CranberryRocker said:

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

Whether you take it once weekly or split it, the area under the curve and the average level come out the same.

The usual thinking is that peaks are what cause sides, while troughs need to stay high enough to keep efficacy.

Mid-February was my start point at 262lbs; I'm at 227lbs now, and lately the scale has been stubborn... the same LB keeps coming and going.

I began 7.5mg on 2nd of May — hadn't realized I'd been on it for so long... Suppression definitely doesn't feel anywhere close to what it was before... Perhaps I'll raise the doseage and see how things go, and I'll map it on GLP1 and see...

8 weeks stuck at one dose and nothing coming off — probably time to go up..

 

[Aliakaraza]

Skidude said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

Yeahhh my eating is definitely mixed and a weekend cheat day always happens — nothing wild, no bingeing, just eating out or cooking something u enjoy. Then it hit me that 7.5mg started right at the beginning of May, sooo maybe it's time...

 

[Skidude]

Aliakaraza said:

Skidude said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

Yeahhh my eating is definitely mixed and a weekend cheat day always happens — nothing wild, no bingeing, just eating out or cooking something u enjoy. Then it hit me that 7.5mg started right at the beginning of May, sooo maybe it's time...

This shows how I titrated and what I lost while on Tirz — once 6 weeks had passed at 7.5, I moved up to 9

 

[Aliakaraza]

Skidude said:

Aliakaraza said:

woundcarping said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

If side effects are holding you back, that's one thing—but when they aren't, go ahead and titrate up.

How long have you been at 7.5mg?

What do your stats say—starting, current, and goal?

CranberryRocker said:

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

Whether you take it once weekly or split it, the area under the curve and the average level come out the same.

The usual thinking is that peaks are what cause sides, while troughs need to stay high enough to keep efficacy.

Mid-February was my start point at 262lbs; I'm at 227lbs now, and lately the scale has been stubborn... the same LB keeps coming and going.

I began 7.5mg on 2nd of May — hadn't realized I'd been on it for so long... Suppression definitely doesn't feel anywhere close to what it was before... Perhaps I'll raise the doseage and see how things go, and I'll map it on GLP1 and see...

8 weeks stuck at one dose and nothing coming off — probably time to go up..

I agree with you, mate... I hadn't even noticed I'd been at 7.5mg for that long...

 

[CranberryRocker]

Aliakaraza said:

woundcarping said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

If side effects are holding you back, that's one thing—but when they aren't, go ahead and titrate up.

How long have you been at 7.5mg?

What do your stats say—starting, current, and goal?

CranberryRocker said:

Type your dose into glp plotter and set it against your once-a-week full dose. Overlay the two plots and the difference becomes clear: dosing twice weekly produces smaller peaks and shallower troughs compared with the single weekly full dose. That is why side effects let up. If you want the peak to match, the split dose has to go up a little.

Some people instead wait out the appetite spikes. For me, carbs go hand in hand with a bigger appetite — my guess is a glucose spike setting it off. Still, I don’t cut carbs out completely, because without them I run low on energy and exercise feels harder. A small tweak to dose and diet may be all that’s needed.

I also keep a good amount of fruit and raw carrots on hand for when hunger hits.

Whether you take it once weekly or split it, the area under the curve and the average level come out the same.

The usual thinking is that peaks are what cause sides, while troughs need to stay high enough to keep efficacy.

Mid-February was my start point at 262lbs; I'm at 227lbs now, and lately the scale has been stubborn... the same LB keeps coming and going.

I began 7.5mg on 2nd of May — hadn't realized I'd been on it for so long... Suppression definitely doesn't feel anywhere close to what it was before... Perhaps I'll raise the doseage and see how things go, and I'll map it on GLP1 and see...

Seems like the moment has come to raise the dose

 

[Aliakaraza]

Skidude said:

Aliakaraza said:

Skidude said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

Yeahhh my eating is definitely mixed and a weekend cheat day always happens — nothing wild, no bingeing, just eating out or cooking something u enjoy. Then it hit me that 7.5mg started right at the beginning of May, sooo maybe it's time...

This shows how I titrated and what I lost while on Tirz — once 6 weeks had passed at 7.5, I moved up to 9





View attachment 428

Got it, I'll definitely be raising it. Split dosing is something I'll keep doing, though I'll use the GLP plotter to work out what dose to take.

On a side note, I'm curious how many calories you're taking in? And what does your workout routine look like?

 

[Skidude]

Aliakaraza said:

Skidude said:

Aliakaraza said:

Skidude said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

Yeahhh my eating is definitely mixed and a weekend cheat day always happens — nothing wild, no bingeing, just eating out or cooking something u enjoy. Then it hit me that 7.5mg started right at the beginning of May, sooo maybe it's time...

This shows how I titrated and what I lost while on Tirz — once 6 weeks had passed at 7.5, I moved up to 9





View attachment 428

Got it, I'll definitely be raising it. Split dosing is something I'll keep doing, though I'll use the GLP plotter to work out what dose to take.

On a side note, I'm curious how many calories you're taking in? And what does your workout routine look like?

For activity, my goal was 10k steps each day. Often I'd head out at 10pm just to finish one more loop around the neighborhood. I stayed really committed to hitting that target.

On the food side, I aimed for 1200 kcal daily plus 120g protein, and I usually landed within 100-200 of those numbers.

Tirz makes it easy to do the things you already know will work, even if they never have before.

I also took supplements.

Since I was dropping my intake to under 50% of what it used to be, I thought it made sense to at least pay attention to nutrients, fiber, and protein.

 

[Aliakaraza]

Skidude said:

Aliakaraza said:

Skidude said:

Aliakaraza said:

Skidude said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

When it's out of the ordinary and titration isn't due yet, undereating could be the culprit.

On top of that, satiety tends to be weaker with lots of refined sugars or carbs compared to proteins.

Possibly all you need is a cheat day, or extra protein.

Otherwise, titration may be due..

Still dropping weight?

Yeahhh my eating is definitely mixed and a weekend cheat day always happens — nothing wild, no bingeing, just eating out or cooking something u enjoy. Then it hit me that 7.5mg started right at the beginning of May, sooo maybe it's time...

This shows how I titrated and what I lost while on Tirz — once 6 weeks had passed at 7.5, I moved up to 9





View attachment 428

Got it, I'll definitely be raising it. Split dosing is something I'll keep doing, though I'll use the GLP plotter to work out what dose to take.

On a side note, I'm curious how many calories you're taking in? And what does your workout routine look like?

For activity, my goal was 10k steps each day. Often I'd head out at 10pm just to finish one more loop around the neighborhood. I stayed really committed to hitting that target.

On the food side, I aimed for 1200 kcal daily plus 120g protein, and I usually landed within 100-200 of those numbers.

Tirz makes it easy to do the things you already know will work, even if they never have before.

I also took supplements.

Since I was dropping my intake to under 50% of what it used to be, I thought it made sense to at least pay attention to nutrients, fiber, and protein.

Yep, I had set 1300 calories per day as my target, and while the tirz was working it wasn't hard to stick to. I reckon I'm due for a reset: log everything I eat, track my steps, and so on. That way, at minimum, I'll be able to pinpoint where things are slipping....

 

[CSM-101]

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

According to this doctor, split-dosing is inadvisable because it could cause receptor down-regulation and desensitization. (At the 4 minute mark).

View: https://youtu.be/FjyZSXPrbyk?t=244

 

[Enyola]

Sure, he's got his own motives as well.

Personally, I gave once-weekly dosing a fair shot because of the concern about receptor desensitization, yet it got me nowhere. So sticking with a split schedule felt like choosing the less bad of 2 options.

By the time my receptors have grown tolerant to the largest tirz dose I can tolerate—whether that's an official or unofficial amount—eloralintide will hopefully be easy to get, letting me rest my glp1 and gip receptors for a good stretch, perhaps around a year. Alternating back and forth each year might become a strategy for long-term maintenance. (This is purely my own unproven guess, of course!)

In the meantime, I'm appreciating the quality of life that comes from splitting a proper dose, rather than riding the highs and lows of side effects and food cravings.

Microdosing most of all! It looked promising on paper, but in this case it didn't pan out in practice.

 

[Aliakaraza]

CSM-101 said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

According to this doctor, split-dosing is inadvisable because it could cause receptor down-regulation and desensitization. (At the 4 minute mark).

View: https://youtu.be/FjyZSXPrbyk?t=244

I had no idea this was a real thing... A lot of people have shared positive results from splitting their doses...

 

[CSM-101]

Aliakaraza said:

CSM-101 said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

According to this doctor, split-dosing is inadvisable because it could cause receptor down-regulation and desensitization. (At the 4 minute mark).

View: https://youtu.be/FjyZSXPrbyk?t=244

I had no idea this was a real thing... A lot of people have shared positive results from splitting their doses...

Right, and just so there's no misunderstanding: I'm not taking a side here. I simply wanted to share that piece of information. In my view, his YouTube channel is outstanding.

 

[lessthanhalf]

CSM-101 said:

Aliakaraza said:

Sooooo basically I'm after a bit of guidance and curious about other people's stories.

I'd been using 7.5mg of Tirz compound, but side effects started hitting me, so I went with splitting it into 3.75mg.

The first couple of split shots were fine, side effects eased off and my appetite felt manageable... but these past two doses seem like they've had zero effect on me.

Last night I injected, felt fine in the morning, then by late afternoon today I'm ravenous. I finished my meal, then grabbed extra, and kept eating until guilt kicked in lol!

Maybe bumping up the dose is what I need...

According to this doctor, split-dosing is inadvisable because it could cause receptor down-regulation and desensitization. (At the 4 minute mark).

View: https://youtu.be/FjyZSXPrbyk?t=244

No scientific evidence exists at all for the notion that GLP tolerance develops toward long-term weight loss effects. Gastrointestinal side effect tolerance and slowed gastric emptying develop gradually across several months, yet mean weight remains a flat line through 4 years of follow-up on a stable tirzepatide dose, which could not happen if receptor desensitisation or tolerance were genuine.

The nearest thing to any long-term decline in effectiveness comes from a mouse study in which semaglutide was repeatedly halted and restarted, with the mice permitted to regain weight during the off-drug periods, and each restart of ozempic produced less weight loss over time. That merely hints that repeated stopping and starting could be a poor strategy, and it has never been replicated in humans.

For some strange reason he also appears to favour very low doses, which the science does not support either; it might make sense when only small weight reductions are required, but the evidence is unambiguous that weight loss rises with dose up to the maximum recommended amounts. He ought to read the many scientific papers published on these topics; holding a medical degree, or even working in the field, does not make someone an expert if they do not read the literature.

 

[CSM-101]

Enyola said:

Sure, he's got his own motives as well.

Personally, I gave once-weekly dosing a fair shot because of the concern about receptor desensitization, yet it got me nowhere. So sticking with a split schedule felt like choosing the less bad of 2 options.

By the time my receptors have grown tolerant to the largest tirz dose I can tolerate—whether that's an official or unofficial amount—eloralintide will hopefully be easy to get, letting me rest my glp1 and gip receptors for a good stretch, perhaps around a year. Alternating back and forth each year might become a strategy for long-term maintenance. (This is purely my own unproven guess, of course!)

In the meantime, I'm appreciating the quality of life that comes from splitting a proper dose, rather than riding the highs and lows of side effects and food cravings.

Microdosing most of all! It looked promising on paper, but in this case it didn't pan out in practice.

In his YouTube video, the study links are included that back up what he says about receptor down-regulation and desensitization caused by split dosing.