Intravenous versus oral

III.c.2.2. Intravenous versus oral therapy. Intravenous therapy (IVT) generates maximum, fast, and long lasting efficacy with minimum adverse effects while the efficacy of oral therapy is less, slow and short lasting with more potential for adverse effects. 

Cost-minimization analysis is a tool used to compare two or more treatment alternatives that are assumed to be equal in efficacy. It simply compares the direct and indirect costs of treatment alternatives in dollars and does not consider the outcomes of the treatments (because they are assumed to be the same). Examples could be to compare the costs of intravenous versus oral dosage forms of the same drug or hospital versus home administration of intravenous pain management. 

In the quest for quality data, the question inevitably arises as to how the isolated gut preparation compares with intravenous versus oral administration in vivo or the in situ cannulation of veins draining specific areas of the gut into which the compound(s) has been administrated or in vitro studies that use Ussing chambers or colon adenocarcinoma cells (Caco-2). 

Kashyap A, Wingard J, Cagnoni P, et al. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality. Biol Blood Marrow Transplant 2002 8 493-500. 

Intravenous versus Oral Administration of Plasma Protein. 279... 

Shafi D, Purandare SV, Sathe AV. Iron deficiency anemia in pregnancy intravenous versus oral route. J Obstet Gynaecol India 2012 62(3) 317-21. 

Schwartz JB, Abernethy DR. Responses to intravenous and oral diltiazem in elderly versus younger patients with systemic hypertension. Am J Cardiol 1987 59 1111-7. 

There has been an open, randomized comparison of amphotericin deoxycholate 0.5 mg/kg/day intravenously versus fluconazole 400 mg/day orally for empirical antifungal therapy in neutropenic patients with cancer and fever refractory to broad-spectrum antibiotics (51). Patients with abnormal hepatic or renal function were excluded, as were those with proven or suspected invasive fungal infection. The mean duration of therapy was 8.3 days with amphotericin deoxycholate and 7.9 days... 

Boogaerts M, Winston DJ, Bow EJ, Garber G, Reboli AC, Schwarer AP, Novitzky N, Boehme A, Chwetzoff E, De Beule K Itraconazole Neutropenia Study Group. Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med 2001 135(6) 412-22. 

Thiebaud D, Burckhardt P, Melchior J, Eckert P, Jacquet AF, Schnyder P, Gobelet C. Two years effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause. Osteoporos Int 1994 4(2) 76-83. 

Contreras G, Pardo V, Leclercq B, et al. Maintenance therapy for proliferative forms of lupus nephritis A randomized clinical trial comparing quarterly intravenous cyclophosphamide versus oral mycophenolate mofetil or azathioprine (abstract). J Am Soc Nephrol 2002 13 15A. 

Winston DJ, MaziarzRT, Chandrasekar PH, etal. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients A multicenter, randomized trial. Ann Intern Med 2003 138 705-713. 

Froessler B, Cocchiaro C, Saadat-GUani K, Hodyl N, Dekker G. Intravenous iron sucrose versus oral iron ferrous sulfete for antenatal and postpartum iron deficiency anemia a randomized trial. J Matem Fetal Neonatal Med 2013 26(7) 654-9. 

In the total plasma response approach, the bioavailability of a compound is determined by measuring its plasma concentration at different times (up to weeks) after single or long-term ingestion of the compound from supplements or food sources. Generally, a plasma concentration-versus-time plot is generated, from which is determined the area-under-curve (AUC) value used as an indicator of the absorption of the componnd. Here, the term relative bioavailability is more appropriate since AUC valnes of two or more treatments are usually compared. This is in contrast to absolnte bioavailability for which the AUC value of the orally administered componnd is compared to that obtained with intravenous administration taken as a reference (100% absorption). 

Bourgeois H, Vermorken J, Dark G, Jones A, Fumoleau P, Stupp R, Tourani J, Brain E, Nguyen L, Lefresne F, Puozzo C (2007) Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours. Cancer Chemotherapy and Pharmacology 60 407 113. 

Hirsh V, Desjardins P, Needles BM, Rigas JR, Jahanzeb M, Nguyen L, Zembryki D, Leopold LH (2007) Oral versus intravenous administration of vinorelbine as a single agent for the first-line treatment of metastatic nonsmall cell lung carcinoma (NSCLC) - A randomized phase II trial. American Journal of Clinical Oncology-Cancer Clinical Trials 30 245-251. 

Anesthetized dogs given 50-250mg/kg intravenously immediately showed hypotension, arrest of gut activity, respiratory paralysis, hyperpnea, and moderate methemoglobinemia. Because death was produced with methe-moglobin levels of only 4%, -propyl nitrate intoxication may be caused in part by a direct action on vascular smooth muscle. (It has been noted that the oral toxicity of -propyl nitrate is very low compared with intravenously administered doses, in which mg/kg doses were lethal versus g/kg orally. )... 

For intravenous dosing simulations 60% of the clearance and volume predictions were vfithin twofold of the observed values and the ranking of compounds by predicted versus observed parameters showed correlation coefficients of 0.8 and 0.6 for clearance and volume respectively. For oral dosing simulations, 40% of the predicted AU C values were within twofold of observed values and the mean fold error was 4.1. For compounds with measured solubility less than 0.012 mg/mLonly 10% of predictions were within twofold, while for compounds vfith higher solubility 70% were within twofold [7] (see Figure 10.5). 

Zohar E, EUis M, Ifrach N, Stern A, Sapir O, Eredman B. The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement. Anesth Analg 2004 99 1679-83. 

Pigott TA, HillJL, Gardy TA, et al A comparison of the behavioral effects of oral versus intravenous mCPP administration in OCD patients and the effect of metergoline prior to i.v. mCPP [see comments]. Biol Psychiatry 33 3-14, 1993 Pilowsky R, West M, Chalmers J Renal sympathetic nerve responses to stimulation, inhibition and destruction of the ventrolateral medulla in the rabbit. Neurosci Lett 60 51-55, 1985... 

Any decrease in the total area under the curve for intramuscular or oral versus intravenous administration would represent a decrease in bioavailability based on that route of administration (16). Common factors that influence bioavailability include ... 

Cephalexin Oral, first-generation drug, used for treating skin and soft tissue infections and urinary tract infections Cefuroxime Oral and intravenous, second generation drug, improved activity versus Pneumococcus and Haemophilus influenzae... 

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