N-in-one dosing

Shaffer, J.E., Adkison, K.K., Halm, K., Hedeen, K. and Berman, J. (1999) Use of N-in-One dosing to create an in vivo pharmacokinetics database for use in developing structure-pharmacokinetic relationships. Journal of Pharmaceutical Sciences, 88, 313-318. 

In summary, there are a number of ways to increase pharmacokinetic throughput by using novel study designs of N-in-One dosing, N-in-One analysis, and limited sample time. The decision on whether to use any of these, or to use conventional study design, must be made on the balance between throughput on the one hand and accuracy and confidence in the pharmacokinetic parameters on the other. 

Diphenhydramine is excreted with the urine mainly as diphenylmethoxyacetic acid, partly as the glutamine or glycine conjugate. Other metabolites are formed by hydroxylation and N-dealkylation. A small proportion is also excreted unchanged. Diphenhydramine is eliminated comparatively slowly. Excretion from the organism of 65% of the substance consumed in one dose takes up to 95 h. The excretion of doxylamine is kinetically analogous. 

Figure 7.8 Long-term effects of MDMA on tissue levels of 5-HT (left panel) and DA (right panel) in brain regions. Male rats received three i.p. injections of 1.5 or 7.5 mg/kg MDMA, one dose every 2 h. Saline was administered on the same schedule. Rats were killed 2 weeks after injections, brain regions were dissected, and tissue 5-HT and DA were assayed by HPLC-ECD.112 Data are mean SEM expressed as percent of saline-treated control values for each region, N = 5 rats/group. Control values of 5-HT and DA were 557 24 and 28 4 pg/mg tissue for frontal cortex (CTX), 429 36 and 10,755 780 pg/mg tissue for striatum (STR), and 1174 114 and 4545 426 pg/mg tissue for olfactory tubercle (OT). Significant compared to saline-injected control for each region (P < 0.05 Duncan s).

Amoxicillin component 80-90 mg/kg/day divided twice daily clavulanate component 6.4 mg/kg/day. Amoxici 11 i n-clavu la nate 90 6.4 or 14 1 ratio is available in the United States 7 1 ratio is available in Canada (use amoxicillin 45 mg/kgfor one dose, amoxicillin 45 mg/kg with clavulanate 6.4 mg/kg for second dose). 

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