Parenteral delivery involves injecting drugs directly into the body, bypassing the gastrointestinal tract. This allows for rapid drug onset but also increases safety risks. Parenteral routes include intravenous, intramuscular, and subcutaneous injections. The rate and extent of drug distribution throughout the body depends on factors like blood flow, protein binding, and capillary permeability. Tissues like muscle and fat can experience damage from injection due to their vascular and immune responses. Careful consideration of a drug's pharmacokinetics is important for optimizing parenteral delivery.

1. Parenteral Delivery Strathclyde 2009 annotated

5. Avoiding First Pass effect Heart Gut lumen Liver Circulation i.v. i.m. s.c. Buccal Pulmonary In oral delivery, veins from the gut pass first through the Liver (hepatic portal system). Buccal & Pulmonary avoid this barrier

9. Effect of particle size: penicillin G procaine i.m (Buckwater & Dickison, 1958). 300,000 unit/ml administered to rabbits Serum Conc. (units/ml)

10. Effect of aluminium monostearate in penicillin G procaine suspension . Rabbits 300, 000 units per ml. After Buckwater & Dickison 1958 m.i.c. 0.03 units /ml Serum Conc. (units/ml) 0 1 2 3 4 5 6 7 Days

14. Infant – 75% water

16. The Elderly - 45% water

17. Drug Movement

19. The Importance of a blood supply...

20. This video illustrates movement of material from large vessels to the Capillary bed

23. Other vascular issues Day 1 Day 5

24. Tissue necrosis Day 10 Brown Recluse Spider (Colorado)

27. Drug Plasma Concentration-Time Profile

35. Volume of distribution 10 1 0.1 3 600 mg dose At T 0 , Ct 0 = 3 ug/ml 0 1 2 3 4 Vd = 600/3 = 200 litres If weplot the data on a log axis and extrapolate back to zero, we can estimate the size of the compartment we are draining from

36. Body fat Less VD than predicted for Water soluble drugs: Higher Concentration

37. Body fat More VD than predicted for Lipid soluble drugs: Lower Concentration & slow equilibrium

38. Injection causes damage

39. Tissue reaction after subcutaneous injection of a suspension of insulin crystals Areas of collagen bands and vacuolated tissue

42. Muscle damage after intramuscular injection Necrotic muscle tissue Scarring occurs on the inside as well

44. Injection into buttocks (MRI guided) Treating an area around the pelvis Local to numb pain

47. Parenteral Delivery Unabsorbed drug In solution Membrane Membrane Bound Plasma & ECF ICF Storage Sites Receptors Only unbound, unionised drug can cross membrane Ionised Non Ionised Ionised Non Ionised Ionised Non Ionised

49. REDISTRIBUTION

50. i.m. Injection of [ 131 I] NaI

58. Guanethidine kinetics Plasma Liver Kidney Skeletal muscle Heart muscle Distribution following i.v. administration In this case the drug has been accumulated in a tissue by an active process. Guanethidine accumulates in synaptic vesicles at the neuromuscular junction