Pharmacokinetic considerations

Toxic symptoms may be dose-dependent and merely an exaggeration of the therapeutically desirable response, e.g., the coma of barbiturate overdosage and persistence of muscular paralysis after succinylcholine administration, or an unpredictable effect of the drug upon an organ or tissue remote from that upon which the therapeutic effect is manifested. 

That blood drug measurements can sometimes provide valuable additional information is, however, not seriously in doubt. For some drugs the intensity of the pharmacological action and severity of side-effects correlates much better with the plasma steady-state concentration than with 

VINCENT MARKS, W. EDWARD LINDUP, AND E. MARY BAYLIS 

Even when administered by intramuscular or subcutaneous injection the rate of absorption of drugs from their site of administration varies, not only from individual to individual, but from site to site in the same subject (B13). For the few drugs studied in this way absorption and distribution was quicker and higher blood levels achieved when injections were given into upper rather than lower limbs and proximal to the trunk than distally. 

Most drugs are deactivated or eliminated at a rate proportional to their plasma concentration. This means, all things being equal, that the 

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Greenblatt DJ, Shader RI Dependence, tolerance, and addiction to benzodiazepines clinical and pharmacokinetic considerations. Drug Merab Rev 8 13-28, 1978... 

An attempt to estimate human daily impact of N nitroso compounds is shown in Table I. The apparent intake from food of preformed nitrosamines is comparatively low, at least in these surveys of a Western diet in England (3). The Intake directly to the respiratory tract from smoking could be somewhat larger. However, if the blood levels reported are confirmed as correct, then inputs of up to 700 meg per day of at least N nitrosodimethylamine (NDMA) may be calculated, based on pharmacokinetic considerations of data obtained in animals and extrapolated to man. It should be emphasized that no information is available at present on nitrosamide intake or in vivo formation, largely because of analytical limitations. 

AG De Boer, F Moolenaar, LGJ de Leede, DD Breimer. Rectal drug administration clinical pharmacokinetic considerations. Clin Pharmacokinet 7 285-311, 1982. 

M Mayersohn. Special pharmacokinetic considerations in the elderly. In WE Evans, JJ Schentag, WJ Jusko, eds. Applied Pharmacokinetics Principles of Therapeutic Drug Monitoring. 3rd ed. Vancouver, WA Applied Therapeutics, 1992, pp. 9-1-9-43. 

Thome, R. and Frey, W. 2001. Delivery of neurotrophic factors to the central nervous system - pharmacokinetic considerations. Clinical Pharmacokinetics 40(12), 907-946. 

Data from Fought Pharmacokinetic considerations in prescribing antiepileptic drugs. Epilepsia 2001 42(Suppl 4) 19-23 Leppik IE. Contemporary Diagnosis and Management of the Patient with Epilepsy, 6th ed. Newton, PA Handbooks in Health Care, 2006.02-149 and Bourgeois BED. Pharmacokinetics and pharmacodynamics of antiepiieptic drugs. In WyllieE. ed. The Treatment of Epilepsy, 4th ed. Philadelphia Lippincott Williams 8 Wilkins, 2006 656-669. 

Torchilin, V. P. Pharmacokinetic considerations in the development of labeled liposomes and micelles for diagnostic imaging. Quat. J. Nucl. Med. 1997, 41, 141-153. 

Belluzzi JD, Lee AG, Oliff HS, Leslie FM (2004) Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology 174 389-395 Benowitz NL (1990) Pharmacokinetic considerations in understanding nicotine dependence. CIBA... 

Voiles DF, McGory R. Pharmacokinetic considerations. Grit Care Clin 1999 15(l) 55-75. 

Kinirons MT, Crome P. Clinical pharmacokinetic considerations in the elderly. An update. Clin Pharmacokinet 1997 33(4) 302-12. 

Barry M, Gibbons S, Back D, Mulcahy F. Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharma-cokinet 1997 32 194-209. 

Milsap, R.L. and Szefler, S.J. (1986) Special pharmacokinetic considerations in children. In Evans, W.E., Schentag, J.J., and Jusko, W.J., eds. Applied Pharmacokinetics. Principles of Therapeutic Drug Monitoring. Spokane, WA Applied Therapeutics, Inc., pp. 294-330. 

M. Gumbleton, W. Sneader (1994). Pharmacokinetic considerations in rational drug design. Clinical Pharmacokinetics 26 161. 

DeVane CL, Pollock BG. Pharmacokinetic considerations of antidepressant use in the elderly. J Clin Psychiatry 1999 60(suppl 20) 38-44. 

Alldredge BK. Seizure risk associated with psychotropic drugs clinical and pharmacokinetic considerations. Neurology 1999 53 S68-S75. 

McAuley JW, Anderson GD Treatment of epilepsy in women of reproductive age Pharmacokinetic considerations. Clin Pharmacokinet 2002 41 559. Meldrum BS, Rogawski MA Molecular targets for antiepileptic drug development. Neurotherapeutics 2007 4 18. [PMID 17199015]... 

PBBs and PBDEs tend to accumulate in lipid-rich tissues and are slowly metabolized and eliminated from the body (see Section 3.4). Several methods to enhance the elimination of PBBs from the body have been examined in animals and are also relevant to PBDEs, including the restriction of caloric intake (to reduce total body fat), and the administration of various agents that interact with bile acids including activated charcoal, mineral oil and bile-binding resins such as cholestyramine (Kimbrough et al. 1980 McConnell et al. 1980 Polin and Leavitt 1984 Polin et al. 1985, 1991 Rozman et al. 1982). It should be mentioned, however, that based on the pharmacokinetic considerations discussed in Section 3.8.1, a rapid breakdown... 

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