I dose

I Dose equivalent limit-s tor lens of eye, skin and extremities 50 5... 

D are summarized in Table I. Doses of 4 jug/kg/day or more produced maternal toxicity and 100% embryonic lethality. Two and 1 / g/kg/day treatments were also toxic for the mothers and resulted in reduced number of viable fetuses per litter and reduced fetal weights. Lower doses... 

Ke, L., Eisenhour, C., Bencherif, M., Lukas, R. Effects of chronic nicotine treatment on expression of diverse nicotinic acetylcholine receptor subtypes. I. Dose- and time-dependent effects of nicotine treatment. J. Pharmacol. Exp. Ther. 286 825, 1998. 

I Dosing Regimens for Selected Drug Treatments for Erectile Dysfunction... 

Phase I dose-escalation trials of titanocene dichloride, formulated in maleic acid buffer, have shown that nephrotoxicity is cumulative... 

Table I. Dose Response Assumptions for PCE Case Study...

Phase I dosing of females if childbearing potential requires a Segment II study in at least one species Phase III dosing of this population requires a Segment I study and both Segment II studies. 

Modi S, Stopeck AT, Gordon MS, Mendelson D, SoUt DB, BagateU R, Ma W, Wheler J, Rosen N, Norton L, Cropp GF, Johnson RG Hannah AL, Hudis CA. (2007) Combination of trastuzumab and tanespimycin (17-AAG KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer A phase I dose-escalation study. J Clin Oncol 25 5410-5417. 

Phase I dose-ranging trials in subjects, as opposed to volunteers (e.g. in severely or terminally iU subjects)... 

Koukourakis MI, Bizakis JG, Skoulakis CE, et al. Combined irinotecan, docetaxel and conventionally fractionated radiotherapy in locally advanced head and neck cancer. A phase I dose escalation study. Anticancer Res 1999 19(3B) 2305-2309. 

In a phase I dose escalation study in locally advanced HNC patients, a concomitant regimen of weekly docetaxel and irinotecan and conventional radiotherapy was combined (47). Docetaxel was given over 20 min on d 1, irinotecan was administered as 30 min infusion on d 3. Three docetaxel/irinotecan dose levels were compared 20/25 mg/m2 (level 1), 20/40 mg/m2 (dose level 2), and 25/55 mg/m2 (dose level 3). Severe asthenia resulted in all patients at dose level 3. Myelosuppression was minimal. Complete responses were seen radiologically in 75% of patients and a partial response in 25% of patients. 

Stopeck A. Results of a phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. Proc Am Soc Clin Oncol 2000 19 206 (abst). 

Ad.TNF gene therapy is presently in clinical trials in patients receiving radiotherapy. An open-label, phase I, dose-escalation study of tumor necrosis factor-alpha (TNFerade) gene transfer with radiation therapy for locally advanced, recurrent, or metastatic solid tumors is currently accruing patients and has several endpoints (82), including toxicity and tolerable dose. Pharmacokinetics will be evaluated and biological correlates will determine the histologic response to therapy. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

G Weiss, HJ Laurencot, A MacDonald, PD Duke, K Misra, GM Horton, SE Katz, SM Brady. Determination of sulfadimethoxine withdrawal time from milk. Part I Dosing, sampling, and assay. J AOAC lnt 78 358-371, 1995. 

In 2007, Boocock et al. [2007] were the first to publish a complete phase I dose pharmacokinetic study in humans. Ten healthy volunteers were recruited to consume single doses of oral resveratrol (0.5, 1, 2.5, or 5 g). Consumption of resveratrol did not cause serious adverse events. Analyses of resveratrol and its metabolites were performed by LC-MS/MS. In plasma in all intake doses resveratrol-3-sulfate (56%) was the highest metabolite, the second and third metabolites were monoglucuronides (17 and 23%, respectively), and, finally, the lowest was free resveratrol (5%). Resveratrol was rapidly absorbed, the 7/nax for all metabolites ranged between 0.8 and 2.4 h, although the half-lives of free resveratrol and the conjugated forms remained for a long time in plasma, between 2.9 and 11.5 h. 

Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. 2007. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 16 1246-1252. 

Danson, S., D. Ferry, V. Alakhov, J. Margison, D. Kerr, D. Jowle, M. Brampton, G. Halbert, and M. Ranson. 1994. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced canBerJ. Cancer. 90 2085-2091. 

I. dose-coupling method for collinear H+H2 reaction, Mol. Phys. 22 (1971) 881. 

Gilbert J, Baker SD, Bowling MK, Grochow L, Figg WD, Zabelina Y, Done-hower RC, Carducci MA. A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin Cancer Res 2001 7 2292-2300. 

Chiorean EG et al (2010) A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol 66 441 148... 

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