Pharmacokinetics
Carvedilol is about 25% to 35% bioavailable following oral administration due to extensive first-pass metabolism. Absorption is slowed when administered with food, however, it does not show a significant difference in bioavailability. Taking carvedilol with food decreases the risk of orthostatic hypotension.The majority of carvedilol is bound to plasma proteins (98%), mainly to albumin. Carvedilol is a basic, hydrophobic compound with a steady-state volume of distribution of 115 L. Plasma clearance ranges from 500 to 700 mL/min. Carvedilol is lipophilic and easily crosses the blood–brain barrier in animals, and hence is not thought to be peripherally selective.The compound is metabolized by liver enzymes, CYP2D6 and CYP2C9 via aromatic ring oxidation and glucuronidation, then further conjugated by glucuronidation and sulfation. The three active metabolites exhibit only one-tenth of the vasodilating effect of the parent compound. However, the 4-hydroxyphenyl metabolite is about 13-fold more potent in β-blockade than the parent.The mean elimination half-life of carvedilol following oral administration ranges from 7 to 10 hours. The pharmaceutical product is a mix of two enantiomorphs, R(+)-carvedilol and  S(–)-carvedilol, with differing metabolic properties. R(+)-Carvedilol undergoes preferential selection for metabolism, which results in a fractional half-life of about 5 to 9 hours, compared with 7 to 11 hours for the S(-)-carvedilol fraction. References
Further reading
External links

"Carvedilol". Drug Information Portal. U.S. National Library of Medicine.
For open tibial fractures in children, there is an increasing trend of using orthopedic cast rather than external fixation. Bone grafting is also helpful in fracture repair. However, internal fixation using plates and screws is not recommended as it increase the rate of infection. Amputation is a last resort intervention, and is determined by factors such as tissue viability and coverage, infection, and the extent of damage to the vascular system. Wound management
Early wound closure is recommended to reduce the rates hospital-acquired infection. For Grade I and II fractures, wound can be healed by secondary intention or through primary closure. There is conflicting evident to suggest the effectiveness of Negative-pressure wound therapy (vacuum dressing), with several sources citing a decreased risk in infection, and others suggesting no proven benefit. Epidemiology
Crush injuries are the most common form of injuries, followed by falls from standing height, and road traffic accidents. Open fractures tend to occur more often in males than females at the ratio of 7 to 3 and the age of onset of 40.8 and 56 years respectively. In terms of anatomy location, fractures of finger phalanges are the most common one at the rate of 14 per 100,000 people per year in the general population, followed by fracture of tibia at 3.4 per 100,000 population per year, and distal radius fracture at 2.4 per 100,000 population per year.