Clinical response time

Although a 5- to 15-min interval between epinephrine injections is often recommended, this interval has not been established in randomized controlled trials, and consequently remains somewhat controversial in reality, the optimal time interval depends mainly on the clinical response to the initial epinephrine dose [1,2]. 

Center for Healthcare Technologies at Lawrence Livermore National Laboratory in Livermore, potentially capable to measure pH at or near the stroke site29. The probe is the distal end of a 125 pm fibre tapered up to a diameter of 50 pm. A fluorescent pH-indicator, seminaphthorhodamine-1-carboxylate, is embedded inside a silica sol-gel matrix which is fixed to the fibre tip. Excitation of the dye takes place at 533 nm and the emission in correspondence of the acid (580 nm) and basic (640 nm) bands are separately detected. The use of this ratiometric technique obviates worrying about source fluctuations, which have the same effects on the two detected signals. The pH sensor developed was first characterised in the laboratory, where it showed fast response time (of the order of tens of seconds) and an accuracy of 0.05 pH units, well below the limit of detection necessary for this clinical application (0.1 pH units). The pH sensor was also tested in vivo on rats, by placing the pH sensor in the brain of a Spraque-Dawley rat at a depth of approximately 5 mm30. 

The properties of a pH electrode are characterized by parameters like linear response slope, response time, sensitivity, selectivity, reproducibility/accuracy, stability and biocompatibility. Most of these properties are related to each other, and an optimization process of sensor properties often leads to a compromised result. For the development of pH sensors for in-vivo measurements or implantable applications, both reproducibility and biocompatibility are crucial. Recommendations about using ion-selective electrodes for blood electrolyte analysis have been made by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) [37], IUPAC working party on pH has published IUPAC s recommendations on the definition, standards, and procedures... 

Tursi A, Brandimarte G, Giorgetti G, Nasi G Assessment of orocaecal transit time in different localization of Crohn s disease and its possible influence on clinical response to therapy. Eur J Gastroenterol Hepatol 2003,15 69-74. 

The answer is a. (Hardman, p 510. Katzung, p 467J Fluctuations in clinical response to L-dopa may or may not be related to drug levels (time of last dose). The likelihood of both kinds of fluctuation increases with longer duration of treatment. When these fluctuations are unrelated to... 

The trial entailed retroviral-mediated ex vivo transduction of haematopoietic stem cells from 10 young SCID-X1 sufferers, with subsequent re-infusion of the treated cells. A marked and prolonged clinical response in which the condition was essentially reversed was observed in 9 out of the 10 patients. The prolonged response was likely due to the transduction of pluripotent progenitor cells with self-renewal capacity (Chapter 10). However, the two youngest patients (1 and 3 months old at the time of treatment) developed uncontrolled proliferation of mature T-lymphocytes 30 months and 34 months after gene therapy respectively. 

The ratio, [Li ]/[Li+ut], in human erythrocytes ranges from 0.2-0.9, illustrating a large inter-individual variability however this ratio is relatively constant over long periods of time for individuals and there is evidence that this phenomena is under genetic control [62]. Higher ratios have been reported in patients with affective illnesses compared to healthy subjects [63] and in females compared to males [64]. There have been attempts to correlate the higher Li+ ratio to a better clinical response of patients to Li+ therapy [65]. 

A suggestion to minimize interaction is to hold tube feeding 1-2 hours before and after phenytoin, but this has no proven benefit Adjust tube feeding rate to account for time held for phenytoin administration Monitor phenytoin serum concentrations and clinical response closely Consider switching to IV phenytoin route if unable to reach therapeutic serum concentration Consider holding tube feeding before and after administration... 

Bupropion is usually initiated at 100 mg twice daily, and this dose may be increased to 100 mg three times daily after 3 days. An increase to 450 mg/ day (the ceiling dose), given as 150 mg three times daily, may be considered in patients with no clinical response after several weeks at 300 mg/day. 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

Fig. 13.3 Clinical response, adverse effects, and hematological parameters were determined and correlated with thiopurine methyl transferase (TPMT) enzyme activity and genotype in 106 patients with inflammatory bowel disease. The odds of achieving complete remission (CR) to azathioprine is approx, five times lower if TPMT is greater than 14 units/mL red blood cells (RBCs). (Reproduced from ref 39.)...

A revised clinical trial application evaluation scheme introduced in 1983 aimed for a response time of 45 working days for Phase 1 and early Phase 11 trials, and 80 working days for Phase 11 and Phase 111 trials, but in practice it took... 

Angina Usual initial dose is 80 to 120 mg 3 times/day 40 mg 3 times/day may be warranted if patients may have increased response to verapamil (eg, decreased hepatic function, elderly). Base upward titration of safety and efficacy evaluated about 8 hours after dosing. Increase dosage daily (eg, unstable angina) or weekly until optimum clinical response is obtained. 

Adults-300 mg/day, given 3 times/day. Begin dosing at 200 mg/day, given as 100 mg twice/day. Based on clinical response, this dose may be increased to 300 mg/day, given as 100 mg 3 times/day no sooner than 3 days after beginning therapy. 

Children (younger than 6 years of age) 10 to 20 mg/kg/day 2 or 3 times/day (4 times/day with suspension). Increase weekly to achieve optimal clinical response administered 3 or 4 times/day. 

Oropharyngeal candidiasis - 200 mg/day for 1 to 2 weeks. Vigorously swish the solution in the mouth (10 ml at a time) for several seconds and swallow. For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose of itraconazole is 100 mg twice daily. Expect clinical response in 2 to 4 weeks. Patients may be expected to relapse shortly after discontinuing therapy. Limited data on the safety of long-term use (more than 6 months) of the oral solution are available at this time. 

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