Need input

[Lani]

Here it is---by the way, "clearance" is a better word than "metabolism or metabolize" when speaking about herceptin or other monoclonal antibodies:

Cancer Chemother Pharmacol. 2005 Oct;56(4):361-9. Epub 2005 May 3.
Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic breast cancer.
Bruno R, Washington CB, Lu JF, Lieberman G, Banken L, Klein P.
Source
Pharmacokinetic and Pharmacodynamic Sciences, MS 70 Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
Abstract
PURPOSE:
To characterize the population pharmacokinetics of trastuzumab in patients with metastatic breast cancer.
METHODS:
A nonlinear mixed effect model was based on pharmacokinetic data from phase I, II, and III studies of 476 patients. The phase I study enrolled patients with advanced solid tumors. The phase II and III studies enrolled patients with HER2-positive metastatic breast cancer. Patients in the pivotal phase II and III studies were treated with a 4 mg/kg loading dose of trastuzumab followed by 2 mg/kg weekly for up to 840 days. The model adequately predicted observed trastuzumab concentrations. Model stability and performance were verified using bootstrap simulations. Percentiles, mean, and standard deviation of observed levels were compared with their distributions from 100 replicates of datasets simulated under the model.
RESULTS:
A two-compartment linear pharmacokinetic model best described the data and accounted for the long-term accumulation observed following weekly administration of trastuzumab. Population estimates from the base model for clearance (CL) and volume of distribution of the central compartment (V1) of trastuzumab were 0.225 L/day, and 2.95 L, respectively. Estimated terminal halflife (t1/2) based on the population estimate was 28.5 days. Interpatient variabilities in clearance and volume were 43 and 29%, respectively. The number of metastatic sites, plasma level of extracellular domain of the HER2 receptor, and patient weight were significant baseline covariates for clearance, volume, or both (P<0.005). However, these covariate effects on trastuzumab exposure were modest and not clinically important in comparison with the large inter-patient variability of CL. Concomitant chemotherapy (anthracycline plus cyclophosphamide, or paclitaxel) did not appear to influence clearance.
CONCLUSION:
This population pharmacokinetic model can predict trastuzumab exposure in the long-term treatment of patients with metastatic breast cancer and provide comparison of alternative dosage regimens via simulation.
PMID: 15868146 [PubMed - indexed for MEDLINE]

[Andrea Barnett Budin]

Some great feedback here, Caroline!

Just wanted to say, it was my 27 yrs of hot flashing dripping wet all day every day that I found myself saying to my dghtr, I don't know what to do. I feel like throwing myself out a window.

Now, I live in a one story house, and I wasn't threatening suicide but I was desperate and my dghtr/mother of 3, always busy and preoccupied stopped in my driveway and came around thoughtfully and said, Maybe you should see an endocrinologist.

This is the first wonderful endo lady I am speaking of. She'd come highly recommended and both my husband and I loved her from the start.

It came to my attention that with allllll the many bld tests we have over the yrs, this new doc ran things I'd never imagined before! And it occurred to me that -- WE SHOULD ALL HAVE AN ENDOCRINOLOGIST. I say this knowing that yet another doc is about the last thing any of us want, but...

With adrenals gone amok -- this is what you need.

It was a holistic/chiropractor lady who gave me a supplement that cured my hot flashes after 27 yrs and untold docs and bks digested by me. It had porcine glandular something in it among other things and within 2 mnths I was cured. However, it knocked my already low TSH even lower and I stopped taking it immediately. My TSH has risen to its usual low (?? my norm) and my flashes have not returned.

Before that I was living on Evening Primrose Oil for some relief.

So, Caroline, definitely, please consider seeing a good endocrinologist and doing all that Becky wisely suggested! Amazing that Becky's mom had all those problems and she therefore speaks from intelligence and experience...

And thanks, Lani. I was on H ev wk for 3 yrs. I was offered the triple dosage ev 3 wks deal a yr before I switched (based on studies in France) but ever cautious opted to wait to see if they all lived... Honestly...

But receiving H weekly and then triple dose I recall the doc saying -- 1 hr and I negotiated to an hr and a half. Just didn't feel right... Not that I was looking to spend any additional time in the chemo room, but... My Inner Voice said, Not so fast...

Don't you just love our club?! All these ladies rock. Blessings my Sisters...

Andi