By Andrew Welsh-Huggins

The Associated Press

COLUMBUS, Ohio — U.S. states not only are having an increasingly difficult time getting the injectable drugs to carry out death sentences, they are also paying as much as 10 times more for the chemicals as in years past.

Ohio only has 40 grams of pentobarbital, enough for seven executions scheduled through February, meaning a likely scramble to find enough for the four scheduled beyond that.

Texas, with the country's busiest death chamber, says it has enough for eight more executions but won't comment on supplies past September. It used the drug Thursday night for the execution of Mexican national Humberto Leal for the 1994 rape-slaying of a 16-year-old girl in San Antonio, despite White House pleas for a Supreme Court stay.

Ohio, Texas and several other states switched to pentobarbital from sodium thiopental this year, after the only U.S. manufacturer said it would discontinue production.

Lake Forest, Illinois-based Hospira, which strongly opposed the use of sodium thiopental, better known as sodium pentothal, in executions, stopped manufacturing it altogether. Hospira said it couldn't promise authorities in Italy, where the drug was to be produced, that it could control the product's distribution all the way to the end user to guarantee it wouldn't be used in executions.

States then switched to pentobarbital, but Denmark-based Lundbeck Inc., the only U.S.-licensed maker of the injectable barbiturate, said July 1 it would put the medication off-limits for capital punishment. It announced a new, tightly controlled distribution system, intended to keep the drug out of the hands of prisons while ensuring deliveries to hospitals and treatment centers for therapeutic purposes, as in the treatment of epilepsy.

It's unclear whether states will be able to stockpile any remaining pentobarbital, which is marketed as Nembutal. Lundbeck says it believes little inventory is left for states to purchase following the announcement. And with an expiration date of about two years, states would have to switch by 2013 anyway.

If pentobarbital supplies dry up, executions could be delayed around the U.S. as states look for yet another alternative.

For many states, making a switch requires a lengthy regulatory and review process. And any change typically leads to lawsuits from inmates who claim the substance violates the constitutional ban on cruel and unusual punishment. Lawsuits over pentobarbital are still being heard.

States got sticker shock when they switched to pentobarbital. Ohio used to spend $218 for 5 grams of sodium thiopental, which it used in combination with two drugs and then, beginning in 2009, as a stand-alone injection.

Now, Ohio spends $2,158 for the same 5-gram dose of pentobarbital, or $6,474 for executions in March, April and May.

Ohio prisons spokesman Carlo LoParo said the state had no alternative but to pay the higher price. He wouldn't comment on the state's plans beyond the February execution.

Texas spent $1,273 on the pentobarbital used to execute Cary Kerr in May for raping and killing a woman 10 years ago. That's almost exactly how much the state spent on sodium thiopental for 17 executions in 2010, or $1,224.

Mississippi, Oklahoma and South Carolina are among other states that confirmed the cost spike to The Associated Press.

Lundbeck attributes the high cost to its contract with a U.S.-based manufacturer that produces the drug, along with ongoing upgrades and improvements to the drug.

Pentobarbital, available for use since 1930, is used by doctors as a sedative in some surgeries, as a hypnotic for short-term treatment of insomnia and to control certain types of seizures, such as those associated with bouts of cholera, meningitis and an emergency state of epilepsy.

The drug in powdered form has also been used in legally assisted suicides in Oregon and Washington. That form, which is made by some companies for veterinary use, is not approved for FDA use in humans. States are unlikely to pursue that as an option because of inevitable lawsuits challenging the use of a non-FDA approved medication.

A chemically related version of pentobarbital marketed to veterinarians is also used in combination with other drugs as Somnasol to euthanize animals.

The drug's veterinary use is a bargain compared to lethal injection for humans. A dose of Somnasol capable of putting a 1,000-pound (450-kilogram) horse to sleep costs about $28, said Dr. John Hubbell, professor of veterinary clinical sciences at Ohio State University.

It's also more expensive to put someone to death with pentobarbital than to use it in assisted suicide. In Washington state, a typical dose of pentobarbital in powdered form costs about $400 for a 10-gram dose, twice the amount used in executions, according to Dr. Tom Preston, medical director of Compassion and Choices of Washington, a group supporting assisted suicide .

Lundbeck's announcement should end an increasingly ugly public relations and investment campaign aimed at pressuring the company to block pentobarbital's use in executions.

Reprieve, a London-based human rights group, had urged Lundbeck to ban use of pentobarbital in executions.

Lundbeck, which manufactures the drug at a U.S. facility it won't identify, said it will now sell directly to hospitals using its previous distributor, Dublin, Ohio-based Cardinal Health, to ship the product. Cardinal said it is working with Lundbeck to implement the system through a Cardinal division, Specialty Pharmaceutical Services.

Cardinal will review all orders, something drug manufacturers typically leave up to their distributors. Then hospital officials will have to sign forms stating they won't use the drug for capital punishment or resell it. Violators would be blocked from future access to the drug.

Experts say the "drop-ship" system Lundbeck is adopting is an established way to limit drug distribution.

"This in essence takes the drug out of the standard distribution system and gives them more control over how the product is used," said health care analyst Dan Mendelson, founder and CEO of Washington, D.C.-based Avalere Health.

Drug makers ship about 9 percent of their products this way, according to data provided by the Healthcare Distribution Management Association.

Drugs delivered via "drop-ship" typically include expensive cancer treatments that are expensive, difficult to make, or not in high demand.

Such a system protects Lundbeck by letting it prove it's done everything it could to restrict pentobarbital's use, said Dan Steiber, editor of Specialty Pharmacy Times and principal of D2 Pharma Consulting in Plano, Texas.

Lundbeck's action will create accountability in the distribution system, said Nick Calla, vice president of industry relations for Drexel Hill, Pennsylvania-based Community Specialty Pharmacy Network.

"You're putting someone on the hook, someone has to testify this product is not being diverted to a site it's not supposed to be at," Calla said. "For products like this, where there's a direct need not to send it to a certain place, I think it works very well."

Ohio is the only state that uses pentobarbital as a stand-alone dose. Other states use the drug to put inmates to sleep, followed by drugs that paralyze inmates, then stop their hearts.

One possible alternative to pentobarbital is propofol, a powerful anesthetic and one of the drugs implicated in the 2009 death of singer Michael Jackson.

The drug was mentioned as a possible option in documents and testimony in the Kentucky court case that led to the U.S. Supreme Court's 2008 ruling upholding the constitutionality of lethal injection.

Ohio also has a backup method that involves injecting two drugs directly into an inmate's muscles, bypassing the veins. Under that method, the sedative midazolam would be followed by the painkiller hydromorphone.

The method has never been used, however, and it comes with potential problems: state officials previously warned reporters that the drugs could cause convulsions or vomiting in inmates.

Oklahoma became the first state to use pentobarbital last year, and Georgia, Ohio, South Carolina and Texas were among states that soon followed suit.

The drug has been used in 18 executions this year.